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References On the Administration of Analgesics Using the ALZET^® Osmotic Pumps

1. Acetylsalicylic Acid

P4829 Yuan,M, Konstantopoulos,N, Lee,J, Hansen,L, Li,Z.-W, Karin,M, Shoelson,S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 2001; 293(--):1673-1677. >>> Acetylsalicylic acid; Salicylate, sodium;; SC; Rat; mice; 2002; 2ML2; 3-4 weeks; Controls received mp w/ vehicle; 2ML2 used in rats, 2002 used in mice; acetylsalicylic acid also called aspirin: dose was 120 mg/kg/day; diabetes (type II).

P0455 Oshima,T., McCluskey,E.R., Honda,A., Needleman,P. Pharmacological manipulation of canine cyclooxygenase and thromboxane synthetase in vivo: differential renal and platelet recovery rates. J.Pharmacol.Exp.Ther. 1984; 229(-2-):598-602. >>> Acetylsalicylic acid; DMSO; Saline; IV (superficial cervical vein); dog; 2ML1; 3 days; pumps primed for 4 hrs. before implant; used prefilled catheter in vein; greater solubility of ASA in DMSO allowed greater concentration in smaller total volume.

2. Alfentanil

P1206 Fujinaga,M., Mazze,R.I., Jackson,E.C., Baden,J.M. Reproductive and teratogenic effects of sufentanil and alfentanil in sprague-dawley rats. Anesth.Analg. 1988; 67(--):166-169. >>> Alfentanil; Sufentanil; Saline; SC; rat (pregnant); 2ML2; 14 days; controls received mp w/ saline; dose-response (text); 3 doses of sufentanil infused; agents infused separately; author states 'in terms of experimental design, the cost of using sc implanted osmotic minipumps is small'; teratology.

3. Aminopyrine

P3395 Kuwahara,S.K., Shinn,T.J., Schreider,B.D., Phan,M.L., Kotake,A.N. Aminopyrine infusion breath test for the determination of changes in P450 metabolism in vivo. Xenobiotica 1995; 25(-9-):973-980. >>> Aminopyrine; Formate, sodium; radio-isotopes; 14C tracer; water, acidified; NaOH; SC; rat; 2001; no duration posted; stability of [N-dimethyl-14C] aminopyrine verified by radiochromatographic analysis- no decomposition observed.

P1268 Azri,S., Renton,K.W. Depression of murine hepatic mixed function oxidase during infection with listeria monocytogenes. J.Pharmacol.Exp.Ther. 1987; 234(-3-):1089-1093. >>> Aminopyrine; Radio-isotopes; 14C tracer; Saline; SC; mice; 2002; 7 days; animals infected with listeria monocytogenes.

4. Antipyrine

R0077 Ray,N., Theeuwes,F. Implantable osmotically powered drug delivery systems. In 'Drug Delivery Systems: Fundamentals and Techniques,' P.Johnson and J.G.Lloyd-Jones (eds.), Ellis Horwood Ltd., Chichester, England and VCH Verlasgesellschaft mbH, Weinheim, Federal Republic of Germany 1987; (-Ch. 7-):120-138. >>> Antipyrine; bleomycin; dopamine HCl; melatonin; methotrexate, sodium; nicotine; prednisolone; radio-isotopes; valproic acid; 14C tracer; 3H tracer; IA; IP; SC; Mice, rabbit, rat; no duration posted; ALZA-authored; synoptic review of mp; post op. care (antibiotic); comparison of sc injections vs. mp infusion; pulsed delivery.

P0592 Sendelbeck,S.L., Urquhart,J. Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion. Brain Research 1985; 328(--):251-258. >>> Antipyrine; Dopamine HCl; Methotrexate, sodium; Radio-isotopes; 14C tracer; 3H tracer; CSF, artificial; Sodium fluorescein; CSF/CNS (diencephalon); rabbit; 2001; 6 days; comparison of agents effects; mp primed in saline 16 hr. prior to implant; stability of labelled&unlabelled Dop.&MTX tested by paper chromat. after 7 days at 37C; brain tissue distribution;.

5. Buprenorphine

P8265 Sorge,R.E., Stewart,J. The effects of long-term chronic buprenorphine treatment on the locomotor and nucleus accumbens dopamine response to acute heroin and cocaine in rats. Pharmacology Biochemistry and Behavior 2006; 84(-2-):300-305. >>> Buprenorphine HCL; SC; Rat; 2ML2; 14, 28 days; Controls received sham surgery; dose-response (fig. 2); pumps replaced after 14 days; half-life (pg. 300) long half-life; tolerance; animal info (male, Long-Evans, 325-350g.).

P8264 Sorge,R.E., Stewart,J. The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. Psychopharmacology 2006; 188(-1-):28-41. >>> Buprenorphine; SC; Rat; 2ML2; 28 days; Controls received sham surgery; functionality of mp verified by plasma buprenorphine levels; dose-response (fig. 1); pumps replaced after 14 days; no stress (see pg. 29); dependence; animal info (male, Long-Evans, 300-350g.).

P7423 Sorge,R.E., Rajabi,H., Stewart,J. Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement. Neuropsychopharmacology 2005; 30(-9-):1681-1692. >>> Buprenorphine; CSF/CNS (nucleus accumbens); Rat; 2ML2; ; Controls received incision and pocket, no pump; dependence; post op. care (antibiotic injection); animal info (male, long-evans, 350-375 g); Plastics One 20G cannula used.

P7403 D'Elia,M., Patenaude,J., Hamelin,C., Garrel,D.R., Bernier,J. Corticosterone binding globulin regulation and thymus changes after thermal injury in mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2005; 288(-5-):E852-E860. >>> Buprenorphine; SC; Mice; 12 hours; Pain treatment.

P6955 Patenaude,J., D'Elia,M., Hamelin,C., Garrel,D., Bernier,J. Burn injury induces a change in T cell homeostasis affecting preferentially CD4+ T cells. Journal of Leukocyte Biology 2005; 77(-2-):141-150. >>> Buprenorphine; Mice; 1,5,10 days.

P6947 Martucci,C., Panerai,A.E., Sacerdote,P. Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses. Pain 2004; 110(-1-2-):385-392. >>> Fentanyl; buprenorphine; Water; SC; Mice; 2001D; 3,7 days; 24 hours; Controls received mp w/ saline; citation may have incorrectly labeled a 2001 pump as the 2001D. "The drugs were delivered with osmotic minipumps, that allowed to reach steady plasma drug concentration for a prolonged period of time, resembling the transdermal route of administration in the human." (p. 386).

P6850 Hou,Y.N., Yuri,T.A., Belcheva,M.M., Clark,A.L., Zahm,D.S., Coscia,C.J. Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling. DEVELOPMENTAL BRAIN RESEARCH 2004; 151(-1-2-):149-157. >>> Buprenorphine; naloxone; methadone; SC; Rat (pregnant); 2ML4; ; Controls received mp w/ water; dose-response (fig. 3); teratology.

P6563 Babin,M.C., Ricketts,K.M., Gazaway,M.Y., Lee,R.B., Sweeney,R.E., Brozetti,J.J. A combination drug treatment against ocular sulfur mustard injury. JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY 2004; 23(-1-):65-75. >>> Buprenorphine HCl; SC; Rabbit; 2ML1; 5-7 days; "The implanted pump provided pain control for 5-7 days without having to administer multiple injections." (p.67).

P6126 D'Elia,M., Patenaude,J., Hamelin,C., Garrel,D.R., Bernier,J. No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters. CLINICAL IMMUNOLOGY 2003; 109(-2-):179-187. >>> Buprenorphine; Saline; IP; Mice; 10 days; Controls received mp w/ vehicle; functionality of mp verified by ability of mu receptor agonist drugs to potentiate; pentobarbital-induced hypothermia. p. 180; pump model not stated.

P7118 Gilberto,D.B., Motzel,S.L., Bone,A.N., Burns,C.L., Zeoli,A.H., Lodge,K.E., Goode,T.L. Use of three infusion pumps for postoperative administration of buprenorphine or morphine in dogs. JAVMA 2002; 220(-11-):1655-1660. >>> Buprenorphine; SC; Dog; 2ML1; 48 hours; Functionality of mp verified by residual volume and serum buprenorphine levels; comparison of infudisk, pegasus vs. ALZET vs. mp; multiple pumps per animal (3,4); mp primed overnight in sterile saline; paper provides list of most possible negative outcomes. Upon pump removal the incisions were closed with tissue glue; ALZET pump was the most cost effective method.

P5702 Borde,V.D., Bernier,J., Garrel,D.R. Effects of dietary fatty acids on burn-induced immunosuppression. Cellular Immunology 2002; 220(-2-):116-124. >>> Buprenorphine; SC; Mice; ; Pain control.

P5301 Robinson,S.E., Wallace,M.J. Effect of perinatal buprenorphine exposure on development in the rat. J Pharmacol Exp.Ther 2001/8; 298(-2-):797-804. >>> Buprenorphine HCl; Methadone HCl; Water, sterile; SC; Rat (pregnant); 28-39 days; Controls received mp w/ vehicle; toxicology; teratology; some pumps replaced after 28 days.

P5008 Robinson,S.E., Wallace,M.J. Effect of perinatal buprenorphine exposure on development in the rat. Journal of Pharmacology and Experimental Therapeutics 2001; 298(--):797-804. >>> Buprenorphine; Methadone; Water; SC; rat (pregnant); rat (neonate); 14, 28 days; controls received mp w/ vehicle; dose-response (graphs p. 802); teratology; toxicology; dependence; 28-day pumps implanted in pregnant rats; 14-day pumps implanted in 10-day old rat pups..

P3551 Hutchings,D.E., Hamowy,A.S., Williams,E.M., Zmitrovich,A.C. Prenatal administration of buprenorphine in the rat: effects on the rest-activity cycle at 22 and 30 days of age. Pharmacol.Biochem.Behav. 1996; 55(-4-):607-613. >>> Buprenorphine; Water, sterile; SC; rat (pregnant); no duration posted; controls received mp w/ sterile water or no treatment; toxicology; teratology.

P3348 Hutchings,D.E., Zmitrovich,A.C., Hamowy,A.S., Liu,P.-Y.R. Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat. Neurotoxicol.Teratol. 1995; 17(-4-):419-423. >>> Buprenorphine; Water, sterile; SC; rat (pregnant); 14 days; controls received mp w/water or no treatment; toxicology; teratology.

P1787 Evans,R.G., Olley,J.E., Rice,G.E., Abrahams,J.M. Effects of subacute opioid administration during late pregnancy in the rat on the initiation, duration and outcome of parturition and maternal levels of oxytocin and arginine vasopressin. Clin.Exp.Pharmacol.Physiol. 1989; 16(--):169-178. >>> Bremazocine; Buprenorphine; Methanol; SC; rat; 2001; no duration posted; paper states the model 2001 released at 2.8 ul/hr which is unlikely.

T0009 Kistler,P. Zur schmerzbekampfung im tierversuch: Eine studie zur wahl geeigneter analgetika fur die schmerzbekampfung bei versuchstieren. Dissertation, Universitat Bern, Zurich 1988; (--):-. >>> D16949; Flupirtine; Tramadol; Buprenorphine; Nalbuphine; SC; mice; rat; 2-7 weeks; German with English abstract (p. 7), pump cross-section and dimensions (pg. 94).

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

6. Butorphanol

P7657 Lee,S.Y., Jang,C.G. Increases in 3H-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPA receptor binding and mRNA expression of AMPA-sensitive glutamate receptor A GluR-A subunits in rats withdrawn from butorphanol. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES 2005; 68(-23-24-):2163-2174. >>> Butorphanol tartrate; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ saline; dependence; animal info (male, Sprague-Dawley 230-250 g).

P7624 Tanaka,S., Fan,L.W., Tien,L.T., Park,Y., Liu-Chen,L.Y., Rockhold,R.W., Ho,I.K. Butorphanol dependence increases hippocampal kappa-opioid receptor gene expression. Journal of Neuroscience Research 2005; 82(-2-):255-263. >>> Butorphanol tartrate; Saline, physiological; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ vehicle; dependence; post op. care (procaine penicillin G; animal info (male, Sprague-Dawley, 250-275 g).

P7059 Kim,S.Y., Chudapongse,N., Lee,S.M., Levin,M.C., Oh,J.T., Park,H.J., Ho,I.K. Proteomic analysis of phosphotyrosyl proteins in the rat brain: Effect of butorphanol dependence. Journal of Neuroscience Research 2004; 77(-6-):867-877. >>> Butorphanol tartrate; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ saline; functionality of mp verified by residual drug volume; dependence; post op. care (procaine penicillin G); stadol; mp primed overnight at 35 degree C in sterile saline.

P6118 Kim,D.S., Lim,H.K., Jang,S.Y., Oh,S. Changes of the level of G protein alpha-subunit mRNA by tolerance to and withdrawal from butorphanol. Neurochemical Research 2003; 28(-12-):1771-1778. >>> Butorphanol; Saline; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ vehicle; tolerance; guide cannula used (10mm); solution was filter sterilized.

P5962 Fan,L.W., Tien,L.T., Tanaka,S., Ma,T., Chudapongse,N., Sinchaisuk,S., Rockhold,R.W., Ho,I.K. Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol. Neuroscience 2003; 121(-4-):1063-1074. >>> Butorphanol; morphine; Saline, sterile; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; dependence; post op. care (penicillin, 0.5% sensorcaine in wound site); guide cannula with stylet was used; dental cement used to adhere cannula to skull; protective aluminuim cap was placed around the cannula; tygon tubing was used; solutions were filter sterilized during filling of the pumps; brain diagram (p. 1066).

P6208 Fan,L.W., Tanaka,S., Tien,L.T., Ma,T.G., Rockhold,R.W., Ho,I.K. Withdrawal from dependence upon butorphanol uniquely increases kappa1-opioid receptor binding in the rat brain. Brain Research Bulletin 2002; 58(-2-):149-160. >>> Butorphanol tartrate; morphine; Saline, sterile physiological; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual drug volume; good methods (p. 150); dependence; post op. care (sensorcaine, procaine penicillin G); guide cannula&stylet used; dental cement secured cannula.

P6207 Fan,L.W., Tanaka,S., Park,Y., Sasaki,K., Ma,T.G., Tien,L.T., Rockhold,R.W., Ho,I.K. Butorphanol dependence and withdrawal decrease hippocampal K-2-opioid receptor binding. Brain Research 2002; 958(-2-):277-290. >>> Butorphanol tartrate; Saline, sterile physiological; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; good methods (p. 279); dependence; post op. care (sensorcaine, procaine penicillin).

P5743 Jang,So Yong., Kim,Younghwa, Oh,Seikwan. The bindings of [3H]muscimol and [3H]flunitrazapam are elevated in discrete brain regions of butorphanol-withdrawal rats. Neurochem Res 2002; 27(-9-):939-946. >>> Butorphanol; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ saline; tolerance; dependence.

P5479 Sinchaisuk,S., Ho,I.K., Rockhold,R.W. Focal kappa-opioid receptor-mediated dependence and withdrawal in the nucleus paragigantocellularis. Pharmacology Biochemistry and Behavior 2002; 74(-1-):241-252. >>> Morphine sulfate; butorphanol tratrate; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ saline; dependence; minipumps were inserted 6-10 days after guide cannula implantation; stylet used.

P5000 Tokuyama,S., Zhu,H., Oh,S., Ho,I.K., Yamamoto,T. Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids. NEUROCHEMISTRY INTERNATIONAL 2001; 39(--):103-109. >>> Morphine; Butorphanol; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/ vehicle; good methods (p. 104-105); dependence; opioid agonists; cannula placement assessed by the presence of CSF in the guide cannula; stylets used to maintain cannula patency during 1-week recovery period;.

P5245 Tokuyama,S., Ho,I.K., Yamamoto,T. A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats. Brain Res Bull. 2000/7/15; 52(-5-):363-369. >>> Morphine; Butorphanol; H7; Saline; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ vehicle; enzyme inhibitor; dependence; H7 is a protein kinase C inhibitor; tygon tubing used; one week recovery period; guide cannula with stylet used to ensure patency; concomitant infusion of H7 and opioids performed by mixing agents in the same pump.

P4310 Jang,C.-G., Rockhold,R.W., Ho,I.K. Withdrawal from butorphanol dependence alters binding of [3H]phorbol dibutyrate to protein kinase C, but not of [3H]forskolin to adenylate cyclase. Brain Research 1999; 821(--):520-525. >>> Butorphanol;; Saline;; CSF/CNS;; rat;; 2ML1;; 3 days;; controls received mp with vehicle; dependence; animals were allowed a 7 day recovery period before infusion began; vehicle was filter sterilized; infusion stopped by snipping the catheter connected to the ICV cannula;.

P4172 Tokuyama,S., Zhu,H., Wakabayashi,H., Feng,Y.Z., Ho,I.K. The role of glutamate in the locus coeruleus during opioid withdrawal and effects of H-7, a protein kinase inhibitor, on the action of glutamate in rats. J.Biomed.Sci. 1998; 5(--):45-53. >>> Morphine; Butorphanol; H7; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/vehicle; cannula placement verified by presence of CSF; stylets were placed in guide cannula to maintain patency; one week recovery period; agents infused singly or concomitantly; dependence.

P4316 Feng,Y., Rockhold,R.W., Ho,I.K. Nor-binaltrophimine precipitates withdrawal and excitatory amino acid release in the locus ceruleus of butorphanol-but not morphine-dependent rats. Journal of Pharmacology and Experimental Therapeutics 1997; 283(-2-):932-938. >>> Butorphanol; Morphine;; Saline;; CSF/CNS;; rat;; 2001; 3 days;; controls received mp with vehicle; good methods; dependence; animals allowed 1 week recovery before infusion began; all solutions were passed through a sterile filter; catheter tubing disconnected to stop drug infusion;.

P4173 Tsang,B.K., He,Z., Wongchanapai,W., Coleman,E.C., Ho,I.-K., Eichhorn,J.H. Induction of tolerance to intrathecal butorphanol in rats. Acta Anesthesiol.Sin. 1997; 35(--):237-240. >>> Butorphanol; Saline; CSF/CNS (spinal cord, intrathecal); rat; 2001; 96 hours; controls received mp w/saline; dose-response (p. 238); tolerance.

P4186 Tokuyama,S., Ho,I.K. Inhibitory effects of diltiazem, an L-type Ca2+ channel blocker, on naloxone-increased glutamate levels in the locus coeruleus of opioid-dependent rats. Brain Research 1996; 722(--):212-216. >>> Butorphanol; Morphine; Diltiazem; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/saline; microdialysis; cannula placement verified visually by cutting vertically through cannula mark on the surface of the cortex; guide cannula implanted; dependence.

P3467 Hoshi,K., Ma,T., Ho,I.K. Precipitated k-opioid receptor agonist withdrawal increases glutamate in rat locus coeruleus. Eur.J.Pharmacol. 1996; 314(--):301-306. >>> Butorphanol tartrate; U-69593; Ethanol; Saline; CSF/CNS; rat; 2001; 2ML1; 3 days; controls received vehicle infusion; dependence.

P3419 Tokuyama,S., Wakabayashi,H., Ho,I.K. Direct evidence for a role of glutamate in the expression of the opioid withdrawal syndrome. Eur.J.Pharmacol. 1996; 295(--):123-129. >>> Morphine; Butorphanol; CSF/CNS; rat; 2001; 3 days; no comment posted.

P3336 Feng,Y.Z., Zhang,T., Tokuyama,S., Zhu,H., Rockhold,R.W., Ho,I.K. m- and d-opioid receptor antagonists precipitate similar withdrawal phenomena in butorphanol and morphine dependence. Neurochem.Res. 1996; 21(-1-):63-71. >>> Butorphanol tartrate; Morphine HCl; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/saline; dependence; animals allowed 1 week recovery after cannulae placement-stylet maintained cannulae patency; bupivacaine given for post-operative pain relief.

P3332 Tokuyama,S., Feng,Y., Wakabayashi,H., Ho,I.K. Possible involvement of protein kinases in physical dependence on opioids: studies using protein kinase inhibitors, H-7 and H-8. Eur.J.Pharmacol. 1995; 284(--):101-107. >>> Morphine HCl; Butorphanol tartrate; H7; H8; CSF/CNS; rat; 2001; 3 days; controls received mp w/saline; dependence; stylet maintained cannula patency during 1 week recovery period; opioid&H7 or H8 given concomitantly.

P2874 Jaw,S.P., Makimura,M., Oh,K.W., Hoskins,B., Ho,I.K. Involvement of k-opioid receptors in opioid dependence/withdrawal: studies using butorphanol. Eur.J.Pharmacol. 1994; 257(--):153-160. >>> Butorphanol tartrate; CSF/CNS; rat; 2001; 3 days; controls received mp with saline; dependence; animals allowed to recover 1 week after cannulation before pump implanted; butorphanol is an opioid agonist/antagonist.

P2769 Narita,M., Feng,Y., Makimura,M., Hoskins,B., Ho,I.K. A protein kinase inhibitor, h-7, inhibits the development of tolerance to opioid antinociception. Eur.J.Pharmacol. 1994; 271(--):543-545. >>> Morphine; Butorphanol; H7; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/saline; tolerance; enzyme inhibitor; H7 administered alone or concomitantly w/morphine and butorphanol in the same pump; one week recovery allowed after icv surgery.

P2754 Feng,Y.Z., Tseng,Y.T., Jaw,S.P., Hoskins,B., Ho,I.K. Tolerance development to butorphanol: comparison with morphine. Pharmacol.Biochem.Behav. 1994; 49(-3-):649-655. >>> Butorphanol; Morphine; Saline, sterile; CSF/CNS; rat; 2001; 1-3 days; controls received mp w/ saline; tolerance; continuous ICV infusion w/ mp "requires minimal pharmacokinetic considerations such as drug metabolism and protein binding . . ." (pg. 654).

P2753 Feng,Y.Z., Narita,M., Tseng,Y.T., Hoskins,B., Ho,I.K. Crosstolerance between butorphanol and morphine in rats. Pharmacol.Biochem.Behav. 1994; 49(-3-):657-661. >>> Butorphanol; Morphine; Saline, sterile; CSF/CNS; rat; 2001; 3 days; controls received mp w/ saline; tolerance.

P3674 Jaw,S.P., Hoskins,B., Ho,I.K. Involvement of d-opioid receptors in physical dependence on butorphanol. Eur.J.Pharmacol. 1993; 240(--):67-72. >>> Butorphanol tartrate; CSF/CNS; rat; 2001; 3 days; 300,000 units of procaine penicillinG given sc post-surgically and allowed one week to recover before infusion; dependence.

P3666 Jaw,S.P., Makimura,M., Hoskins,B., Ho,I.K. Effects of nor-binaltorphimine on butorphanol dependence. Eur.J.Pharmacol. 1993; 239(--):133-140. >>> Butorphanol tartrate; CSF/CNS; rat; 2001; 3 days; controls received saline injections; dependence; 300,000 units of procaine penicillin G given SC after cannula placement and animals given 1 week to recover before drug infusion; butorphanol filtered before infusion.

P2324 Jaw,S.P., Hoskins,B., Ho,I.K. Opioid antagonists and butorphanol dependence. Pharmacol.Biochem.Behav. 1993; 44(--):497-500. >>> Butorphanol tartrate; CSF/CNS; rat; 2001; 3 days; dependence.

P2381 Oh,K.W., Makimura,M., Jaw,S.P., Hoskins,B., Ho,I.K. Effects of B-funaltrexamine on butorphanol dependence. Pharmacol.Biochem.Behav. 1992; 42(--):29-34. >>> Butorphanol tartrate; CSF/CNS; rat; 2001; 72 hours; dependence.

P3157 Horan,P., Ho,I.K. The physical dependence liability of butorphanol: a comparative study with morphine. Eur.J.Pharmacol. 1991; 203(--):387-391. >>> Butorphanol tartrate; Morphine sulfate; CSF/CNS; rat; 2001; 3 days; controls received mp with saline; animals allowed 1 week recovery after cannula placement -- stylet maintained cannula patency; dependence.

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

7. Codeine

P4917 Chew,M., White,J.M., Somogyi,A.A., Bochner,F., Irvine,R.J. Precipitated withdrawal following codeine administration is dependent on CYP genotype. European Journal of Pharmacology 2001; 425(--):159-164. >>> Morphine tartrate; Codeine phosphate; Saline; SC; rat; 2ML1; 7 days; functionality of mp verified by plasma drug levels; dose response (graphs p. 161); dependence.

8. F13640

P7681 Colpaert,F.C., Deseure,K., Stinus,L., Adriaensen,H. High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning. Journal of Pharmacology and Experimental Therapeutics 2006; 316(-2-):892-899. >>> F13640; morphine, HCl; Saline; SC; Rat; 2ML2; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every two weeks; multiple pumps per animal (2); animal info (male, Sprague-Dawley, 220-240 g); during pump replacement a new incision was made about 1 cm away from the previous incision.

P6803 Colpaert,F.C., Wu,W.P., Hao,J.X., Royer,I., Sautel,F., Wiesenfeld-Hallin,Z., Xu,X.J. High-efficacy 5-HT1A receptor activation causes a curative-like action on allodynia in rats with spinal cord injury. European Journal of Pharmacology 2004; 497(-1-):29-33. >>> F13640; SC; Rat; 2ML4; 56 days; Controls received mp w/ saline; functionality of mp verified by plasma levels; long-term study; pumps replaced at day 28; 5-HT1A receptor agonist; spinal cord injury; pain.

P6234 Wu,W.P., Hao,J.X., Xu,X.J., Wiesenfeld-Hallin,Z., Koek,W., Colpaert,F.C. The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury. European Journal of Pharmacology 2003; 478(-2-3-):131-137. >>> F13640; SC; Rat; 2ML4; 56 days; Controls received mp w/ saline; functionality of mp verified by F13640 plasma levels; long-term study; pumps replaced (after 28 days).

P5902 Deseure,K., Koek,W., Adriaensen,H., Colpaert,F.C. Continuous administration of the 5-hydroxytryptamine 1A agonist (3-ch loro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]-methadone (F 13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-2-):505-514. >>> F13640; F13714; morphine; bacioten; Saline; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; Post Op. Care (aerosol bandage applied to protect against bacterial contamination); F13640 is a novel analgesic&5-HT1A receptor agonist; behavorial study; F13640, F13714&morphine were infused in one pump; bacioten infused in two pumps due to limited solubility; contro.

P5716 Slot,L.A.B., Koek,W., Tarayre,J.P., Colpaert,F.C. Tolerance and inverse tolerance to the hyperalgesic and analgesic actions, respectively, of the novel analgesic, F 13640. European Journal of Pharmacology 2003; 466(-3-):271-279. >>> F13640; Water, distilled; SC; Rat; 2ML2; 5 weeks; Controls received mp w/ saline; dose-response (Fig.2; p.275); pumps replaced every week, F13640 is a novel analgesic; serotonin receptor agonist; post op. care (the site of pump emplacement was massaged daily to avoid tissue adherence).

P6585 Colpaert,F.C., Tarayre,J.P., Koek,W., Pauwels,P.J., Bardin,L., Xu,X.J., Wiesenfeld-Hallin,Z., Cosi,C., Carilla-Durand,E., Assie,M.B., Vacher,B. Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology 2002; 43(-6-):945-958. >>> F13640; morphine HCL; imipramine HCl; ketamine HCl; gabapentin; Water, double distilled; SC; Rat; 2ML2; 14 days; Controls received mp w/ saline; dose-response (fig. 3); comparison of IP&SC injections vs. mp; tolerance; dependence; "Continuous F 13640 infusion uniquely produced profound analgesia in this model of severe, chronic pain." (p. 955).

9. Fentanyl

P8341 Bruijnzeel,A.W., Marcinkiewcz,C., Isaac,S., Booth,M.M., Dennis,D.M., Gold,M.S. The effects of buprenorphine on fentanyl withdrawal in rats. Psychopharmacology 2007; 191(-4-):931-941. >>> Fentanyl citrate salt; Saline, sterile; SC; Rat; 2ML2; 2ML4; 14, 28 days; Controls received mp w/ vehicle; functionality of mp verified by plasma fentanyl concentrations; tolerance; dependence; animal info (male, Wistar, 300-350 grams).

P7446 Gaitan,G., Ahuir,F.J., Herrero,J.F. Enhancement of fentanyl antinociception by subeffective doses of nitroparacetamol (NCX-701) in acute nociception and in carrageenan-induced monoarthritis. LIFE SCIENCES 2005; 77(-1-):85-95. >>> Fentanyl; Saline; SC; Rat; 2ML1; 5 days; Controls received mp w/ vehicle; tolerance; animal info (male, Wistar, 250-320 g).

P7082 Trujillo,K.A., Kubota,K.S., Warmoth,K.P. Continuous administration of opioids produces locomotor sensitization. Pharmacology Biochemistry and Behavior 2004; 79(-4-):661-669. >>> Morphine sulfate; fentanyl; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; comparison of pellets vs. mp; tolerance; mp primed overnight in saline at room temperature; pain; animal info (225-250 grams).

P6947 Martucci,C., Panerai,A.E., Sacerdote,P. Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses. Pain 2004; 110(-1-2-):385-392. >>> Fentanyl; buprenorphine; Water; SC; Mice; 2001D; 3,7 days; 24 hours; Controls received mp w/ saline; citation may have incorrectly labeled a 2001 pump as the 2001D. "The drugs were delivered with osmotic minipumps, that allowed to reach steady plasma drug concentration for a prolonged period of time, resembling the transdermal route of administration in the human." (p. 386).

P6424 Terman,G.W., Jin,W.Z., Cheong,Y.P., Lowe,J., Caron,M.G., Lefkowitz,R.J., Chavkin,C. G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal. British Journal of Pharmacology 2004; 141(-1-):55-64. >>> Fentanyl; SC; Mice (knockout); 1007D; 7 days; Tolerance; behavioral study.

P5909 Morinville,A., Cahill,C.M., Esdaile,M.J., Aibak,H., Collier,B., Kieffer,B.L., Beaudet,A. Regulation of delta-opioid receptor trafficking via mu-opioid receptor stimulation: Evidence from mu-opioid receptor knock-out mice. Journal of Neuroscience 2003; 23(-12-):4888-4898. >>> Fentanyl Citrate; Saline; SC; Rat; 2001; 48 hours; Controls received mp w/ vehicle; analgesic; "because of its reported short half-life and duration of action, fentanyl citrate was also administered chronically via osmotic mini-pumps." p. 4889; multiple pumps per animal (2).

P5623 Holtzman,S.G. Discrimination of a single dose of morphine followed by naltrexone: Substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence. Journal of Pharmacology and Experimental Therapeutics 2003; 304(-3-):1033-1041. >>> Fentanyl; methadone; Saline; water, distilled; SC; Rat; 2ML2; 14 Days; Dependence.

P4915 Fendt,M., Mucha,R.F. Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe for drug-related motivational states. Psychopharmacology 2001; 155(--):242-250. >>> Fentanyl citrate; Saline; SC; rat; 2001; 2002; 4-7 days; controls received placebo "pump-shaped" silicone plugs; good methods (priming p. 244); fentanyl is an opiate analgesic; anxiety; withdrawal precipitated by IV naloxone.

P4632 Lohmann,A.B., Smith,F.L. Buprenorphine substitution ameliorates spontaneous withdrawal in fentanyl-dependent rat pups.. Pediatr.Res. 2001; 49(-1-):50-55. >>> Fentanyl citrate;; Saline, isotonic;; SC;; rat (neonate);; 1003D;; 72 hours;; controls received mp w/ vehicle; teratology; tolerance; dependence; the surgical incision was closed with Vetbond Tissue Adhesive; pumps implanted in 14-day old rat pups..

P4722 Choe,C.H, Smith,F.L. Sedative tolerance accompanies tolerance to the analgesic effects of fentanyl in infant rats.. Pediatr.Res. 2000; 47(-6-):727-735. >>> Fentanyl;; Saline;; rat (neonate);; 1003D;; 3 days;; Controls received mp w/ vehicle; functionality of mp verified by plasma fentanyl levels; dose-response (table p. 729 / graph p. 730); tolerance; dependence; pumps implanted in 14 day old rat pups; surgical incision was closed with Vetbond tissue adhesive (3M animal care products);.

P4328 Thornton,S.R., Lohmann,A.B., Nicholson,R.A., Smith,F.L. Fentanyl self-administration in juvenile rats that were tolerant and dependent to fentanyl as infants. Pharmacology Biochemistry and Behavior 2000; 65(-3-):563-570. >>> Fentanyl HCl;; Saline, pyrogen-free isotonic; SC;; rat (neonate);; 1003D; 3-5 days;; controls received mp with saline; tolerance; dependence; pain.

P4308 Thornton,S.R., Smith,F.L. Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence. European Journal of Pharmacology 1998; 363(--):113-119. >>> Fentanyl HCl;; Saline;; SC;; rat (neonate);; 1003D;; 3-5 days;; controls received mp w/ vehicle; tolerance; dependence;.

P3490 Chan,K.W., Duttory,A., Yoburn,B.C. Magnitude of tolerance to fentanyl is independent of m-opioid receptor density. Eur.J.Pharmacol. 1997; 319(--):225-228. >>> Fentanyl; SC; mice; 2001; 3 days; controls received placebo pellet; tolerance.

P3449 Thornton,S.R., Smith,F.L. Characterization of neonatal rat fentanyl tolerance and dependence. J.Pharmacol.Exp.Ther. 1997; 281(-1-):514-521. >>> Fentanyl; SC; rat (neonate); 1003D; no duration posted; controls received mp w/ saline; excellent methodology for working with neonates; animals were given penicillin G prophylactically, along with .5 ml saline to prevent hypovolemia; pumps were implanted 1.5 cm from the base of the tail to obviate problems w/ nursing; tolerance; dependence; teratology.

P3345 Duttaroy,A., Yoburn,B.C. The effect of intrinsic efficacy on opioid tolerance. Anesthesiology 1995; 82(--):1226-1236. >>> Morphine sulfate; Fentanyl; Etorphine; Saline; SC; mice; 2001; 2002; 7 days; 72 hrs; controls received inert placebos; comparison of SC injections vs. mp; tolerance; "Intrinsic efficacy appears to induce tolerance more significantly after continuous administration than after intermittent administration." p.1235.

P3555 Paronis,C.A., Holtzman,S.G. Sensitization and tolerance to the discriminative stimulus effects of mu-opioid agonists. Psychopharmacology 1994; 114(--):601-610. >>> Naloxone HCl; Morphine sulfate; Meperidine HCl; Fentanyl citrate; Saline; SC; rat; 2ML1; 7 days; controls received sham pumps; tolerance.

P3058 Yoburn,B.C., Duttaroy,A., Shah,S., Davis,T. Opioid antagonist-induced receptor upregulation: effects of concurrent agonist administration. Brain Res.Bull. 1994; 33(-2-):237-240. >>> Naloxone; Fentanyl citrate; Etorphine HCl; NaCl; SC; mice; 2001; 2002; 7-8 days; controls received placebo pellets.

P3060 Yoburn,B.C., Billings,B., Duttaroy,A. Opioid receptor regulation in mice. J.Pharmacol.Exp.Ther. 1993; 265(-1-):314-320. >>> Etorphine HCl; Fentanyl citrate; Naloxone HCl; NaCl; SC; mice; 2001; 2002; 7-8 Days; controls received placebo pellets; dose-response; comparison of sc fentanyl injections vs. mp; good methods; tolerance.

P2408 Paronis,C.A., Holtzman,S.G. Development of tolerance to the analgesic activity of mu agonists after continuous infusion of morphine, meperidine or fentanyl in rats. J.Pharmacol.Exp.Ther. 1992; 262(-1-):1-9. >>> Morphine; Meperidine; Fentanyl; Saline; SC; rat; 2ML1; 1 week; tolerance.

P2169 Ammer,H., Nice,L, Lang,J., Schulz,R. Regulation of G proteins by chronic opiate and clonidine treatment in the guinea pig myenteric plexus. J.Pharmacol.Exp.Ther. 1991; 258(-3-):790-796. >>> Clonidine; Fentanyl; U-50,488H; Saline; SC; guinea-pig; 2001; 2002; 6-14 days; controls received sham op; tolerance; dependence; antihypertensive.

P1885 MacDonald,M.C., Wilkinson,M. Occurence of sexual maturation in chronic opiate-treated female rats. J.Endocrinol. 1991; 129(--):253-259. >>> Fentanyl citrate; SC; rat; 2001; 2002; 14 days; no comment posted.

P1289 Fujinaga,M., Mazze,R.I. Teratogenic and postnatal developmental studies of morphine in Sprague-Dawley rats. Teratology 1988; 38(--):401-410. >>> Fentanyl; Morphine; Saline; SC; rat (pregnant); 2ML2; 15 days; Multiple pumps per animal (2) for high dose group; functionality of mp verified by plasma levels; toxicology/teratology.

P1129 Mazze,R.I., Fujinaga,M., Baden,J.M. Reproductive and teratogenic effects of nitrous oxide, fentanyl and their combination in sprague-dawley rats. Br.J.Anaesth. 1987; 59(--):1291-1297. >>> Fentanyl citrate; Saline; SC; rat (pregnant); 2002; 14 days; controls received mp w/ saline; concomitant administration of nitrous oxide; teratology.

P0962 Fujinaga,M., Stevenson,J.B., Mazze,R.I. Reproductive and teratogenic effects of fentanyl in Sprague-Dawley rats. Teratology 1986; 34(-1-):51-57. >>> Fentanyl; Water; SC; rat; 2002; 2ML4; 6 weeks; controls received mp w/sterile water; 2002 pumps replaced w/2ML4 pumps; teratology; 3 doses of agent infused; long-term study.

P0827 Lux,B., Schulz,R. Effect of cholera toxin and pertussis toxin on opioid tolerance and dependence in the guinea-pig myenteric plexus. J.Pharmacol.Exp.Ther. 1986; 237(-3-):995-1000. >>> Fentanyl dihydrogencitrate; Saline; SC; guinea-pig; 2001; 6 days; pain.

P0617 Vinayek,R., Brown,D.R., Miller,R.J. Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa. J.Pharmacol.Exp.Ther. 1985; 232(-3-):781-785. >>> Enkephalin agonist DADL; Fentanyl citrate; Saline; SC; guinea-pig; 2001; 5 days; comparison of agents effects; controls were sham-operated only; peptides.

P0585 Schulz,R., Seidl,E., Herz,A. Opioid dependence in the guinea-pig myenteric plexus is controlled by non-tolerant and tolerant opioid receptors. Eur.J.Pharmacol. 1985; 110(-3-):335-341. >>> Fentanyl; SC; guinea-pig; 2001; 6 days; morphine given by pellets.

P0482 Schulz,R., Wuster,M., Herz,A. Receptor preference of dynorphin A fragments in the mouse vas deferens determined by different techniques. J.Pharmacol.Exp.Ther. 1984; 230(-1-):200-204. >>> Dynorphin A(1-8); Bestatin; Captopril; Dynorphin A; Enkephalin agonist DADL; Fentanyl; Thiorphan; Saline; SC; vas deferens; Mice; 2001; 2ML1; no duration posted; Comparison of agents effects; 2ML1 pump used w/ captopril, thiorphan, and bestatin; DADL&FEN admin. sc; peptides; antihypertensive.

P0419 Lux,B., Schulz,R. Cholera toxin selectively affects the expression of opioid dependence in the tolerant myenteric plexus of the guinea-pig. Eur.J.Pharmacol. 1983; 96(--):175-176. >>> Fentanyl; SC; guinea-pig; 2001; 6 days; no comment posted.

P0170 Schulz,R., Wuster,M., Rubini,P., Herz,A. Functional opiate receptors in the guinea-pig ileum: their differentiation by means of selective tolerance development. J.Pharmacol.Exp.Ther. 1981; 219(-2-):547-550. >>> DsThr; Enkephalin agonist DADL; Fentanyl; FK-33824; MR-2034; MRZ; Normorphine; Water; SC; guinea-pig; 2001; 6 days; peptides.

10. Flupirtine

T0009 Kistler,P. Zur schmerzbekampfung im tierversuch: Eine studie zur wahl geeigneter analgetika fur die schmerzbekampfung bei versuchstieren. Dissertation, Universitat Bern, Zurich 1988; (--):-. >>> D16949; Flupirtine; Tramadol; Buprenorphine; Nalbuphine; SC; mice; rat; 2-7 weeks; German with English abstract (p. 7), pump cross-section and dimensions (pg. 94).

11. Hydromorphone

P3843 Lesser,G.J., Grossman,S.A., Leong,K.W., Lo,H., Eller,S. In vitro and in vivo studies of subcutaneous hydromorphone implants designed for the treatment of cancer pain. Pain 1996; 65(--):265-272. >>> Hydromorphone; SC;; rabbit;; 2ML4;; 4 weeks;; functionality of mp verified by blood sample assays; comparison of IV bolus administration vs. EVA polymer drug delivery vs. mp; pain; cancer;.

P2556 Kowalski,W., Chatterton,R.T., Kazer,R.R., Wentz,A.C. The impact of subchronic hypercortisolemia on progesterone metabolism and the luteinizing hormone-progesterone axis in the cynomolgus monkey. J.Clin.Endocrinol.Metab. 1993; 77(-6-):1597-1604. >>> Hydrocortisone phosphate; Hydromorphone; Saline; SC; monkey; 2 months; monkeys received both a mp w/ HP and a mp w/ saline on alternating menstrual cycles;.

P0770 Behm,M.C., Stout-Caputi,M.V., Mahalik,M.P., Gautieri,R.F. Evaluation of the teratogenic potential of hydromorphone administered via a miniature implantable pump in mice. Res.Commun.Substance Abuse 1985; 6(-3-):165-177. >>> Hydromorphone; Saline; Water; SC; mice (pregnant); 2001; 4 days; no stress or complications (see pg. 170-71); describes mp as 'valuable tool...' and discusses advantages of this type of delivery system (see pgs. 165, 176); toxicology.

12. Indomethacin

P4819 Babin,M.C., Ricketts,K., Skvorak,J.P., Gazaway,M., Mitcheltree,L.W., Casillas,R.P. Systemic administration of candidate antivesicants to protect against topically applied suitor mustard in the mouse ear vesicant model (MEVM ).. Journal of Applied Toxicology 2000; 20(--):S141-S144. >>> Hydrocortisone; indomethacin; olvanil; PEG 200; SC; mice; 2 days; Controls received mp w/ vehicle; toxicology.

P4475 Zlatnik,M.G., Buhimschi,I, Chwalisz,K., Liao,Q.-P., Saade,G.R., Garfield,R.E. The effect of indomethacin and prostacyclin agonists on blood pressure in a rat model of preeclampsia.. Am.J.Obstet.Gynecol. 1999/5; 180(-5-):1191-1195. >>> Iloprost; Cicaprost; L-NAME; Indomethacin;; Saline;; SC;; rat (pregnant);; 2ML2;; 2 weeks;; controls received mp w/vehicle; comparison of SC injections vs. mp; cardiovascular; L-NAME is a synthase inhibitor;.

P3986 Henke,P.K., Bergamini,T.M., Watson,A.L., Brittian,K.R., Powell,D.W., Peyton,J.C. Bacterial products primarily mediate fibroblast inhibition in biomaterial infection. J.Surg.Res. 1998; 74(--):17-22. >>> Antibody, anti-interferon gamma; Antibody, indomethacin; Antibody, anti-TNFa; Antibody, interleukin 1 alpha; PBS, sterile; ETOH; Indomethacin; SC; mice; 1007D; 7 days; immunology; pump implanted next to Dacron graft; peptides.

P3918 Henke,P.K., Bergamini,T.M., Brittian,K.R., Polk Jr,H.C. Prostaglandin E2 modulates monocyte MHC-II (Ia) suppression in biomaterial infection. J.Surg.Res. 1997; 69(--):372-378. >>> Indomethacin; Antibody, anti-IL-1a; Antibody, anti-TNFa; PBS; ETOH; SC; mice; 7 days; controls received mp w/ vehicle; immunology.

P4207 Shimoda,K., Nomura,M., Kato,M. Effect of antioxidants, anti-inflammatory drugs, and histamine antagonists on Sparfloxacin-induced phototoxicity in mice. Fundam.Appl.Toxicol. 1996; 31(--):133-140. >>> Catalase; Dimethyl sulfoxide; Dexamethasone; Indomethacin; Pyrilamine maleate; AA-861; Cimetidine; Phenidone; Ethanol; Saline; SC; mice; 1007D; 72 hours; all agents infused concomitantly in the same pump; preliminary study conducted to test solubility and toxicity for 5 days; enzyme inhibitors; toxicology.

P3614 Fernandez,M., Garcia-Pagan,J.C., Casadevall,M., Mourelle,M.I., Pique,J.M., Bosch,J., Rodes,J. Acute and chronic cyclooxygenase blockade in portal-hypertensive rats: influence on nitric oxide biosynthesis. Gastroenterol. 1996; 110(--):1529-1535. >>> Indomethacin; Sodium carbonate; SC; rat; 2ML2; 7 days; sonication used to suspend indomethacin.

P2852 Sakamoto,T., Soriano,D., Nassaralla,J., Murphy,T.L., Oganesian,A., Spec,C., Hinton,D.R., Ryan,S.J. Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate. Arch Ophthalmol. 1995; 113(--):222-226. >>> Indomethacin; GBR buffer; Cyclodextrin, B-; Eye (vitreous); monkey; 2ML2; 14 days; control eyes received mp with vehicles; enzyme inhibitor; indomethacin is a cyclooxygenase (COX) inhibitor; detailed description of vitreal cannula implantation; empty pump implanted at time of cannula implantation to allow 1-month recovery period; beta-cyclodextrin used as a carrier molecule; some monkeys served both as control and drug treatment group (different treatment in each eye); a vitreous opacity appeared in some eyes during infusion but disappeared after the pump was disconnected.

P1204 Schlegel,W., Doren,M., Cirkel,U., Schneider,H.P.G. Effect of continuous intrauterine administration of prostaglandin F2alpha and indomethacin on fertilization of rabbits. Horm.Metab.Res. 1986; 18(--):457-461. >>> Indomethacin; Prostaglandin F2a; HCl; Sodium hydroxide; Saline; intrauterine; rabbit; 2002; 11 days; controls received mp w/ vehicle; separate and simultaneous infusion of agents; comparison of agents effects; NaOH, HCl and saline were used in combination as the vehicle for indomethacin; many different exp.; tissue perfusion (cornua of uterus).

P1031 Doktorcik,P.E., Kennedy,T.G. 6-Keto-prostaglandin E1 and the decidual cell reaction in rats. Prostaglandins 1986; 32(-5-):679-689. >>> Indomethacin; Prostaglandin E1; Prostaglandin E2; Ethanol; Gelatin; PBS; intrauterine; rat; 2001; 5 days; mp w/vehicle; dose-response; indomethacin infused with prostaglandin E1 in one group and with prostaglandin E2 in another group; tissue perfusion (uterus).

P0794 Kennedy,T.G. Intrauterine infusion of prostaglandins and decidualization in rats with uteri differentially sensitized for the decidual cell reaction. Biol.Reprod. 1986; 34(-2-):327-335. >>> Indomethacin; Prostaglandin E2; Prostaglandin F2a; Ethanol; Gelatin; PBS; intrauterine; rat; 2001; 5 days; replacement therapy (ovariectomy); controls received mp w/ vehicle; estradiol and progesterone injected sc w/ mp PG infusion; vehicle contained indomethacin to reduce PG synthesis; tissue perfusion (uterus).

P0739 Kennedy,T.G. Evidence for the involvement of prostaglandins throughout the decidual cell reaction in the rat. Biol.Reprod. 1985; 33(--):140-146. >>> Indomethacin; Prostaglandin E2; Prostaglandin F2a; Ethanol; PBS; intrauterine; rat; 2001; 5 days; replacement therapy (ovariectomy); pumps primed overnight in saline; sc adminis. of agents in comb. w/mp infusion; separate and simultaneous infusion of agents; tissue perfusion (uterus).

13. Ketorolac

P5091 Southall,M.D., Bolyard,L.A., Vasko,M.R. Twenty-four hour exposure to prostaglandin downregulates prostanoid receptor binding but does not alter PGE(2)-mediated sensitization of rat sensory neurons. Pain 2002; 96(--):285-296. >>> Ketorolac tromethamine; Saline; CSF/CNS (intrathecal); rat; 2001; 48 hours; controls received mp w/ vehicle; ketorolac is an NSAID sold as Toradol; cannula patency verfied by saline injection.

P4204 Shufflebarger,J.V., Doyle,J., Roth,T., Maguire,K., Rothkopf,D.M. The effect of ketorolac on microvascular thrombosis in an experimental rabbit model. Plast.Reconstr.Surg. 1996; 98(--):140-145. >>> Ketorolac; IV (jugular); rabbit; 2ML1; 7 days; controls received mp w/saline; functionality of mp verified by residual volume; comparison of i.m. injections vs. mp; ketorolac also called Toradol; NSAID.

14. Levorphanol

P2440 Teskey,G.C., Kavaliers,M. Modifications of social conflict-induced analgesic and activity responses in male mice receiving chronic opioid agonist and antagonist treatments. Pharmacol.Biochem.Behav. 1991; 38(--):485-493. >>> Levorphanol tartrate; Naltrexone HCl; U-50,488H; ICI-154,129; Saline; IP; mice; 2001; 7 days; functionality of mp verified by measuring residual pump volume; tolerance.

15. Lofentanil

S0190 Cowan,A., August,D., Harp,J.R., Carlsson,C., Smith,D.S. Acute physical dependence in rats: a comparison of fentanyl, lofentanil and sufentanil. Fed.Proc. 1982; 41(-4-):1220-. >>> Lofentanil; Fentanyl; Sufentanil; SC; rat; 2001; 6 hours; no comment posted.

16. Meperidine

P3555 Paronis,C.A., Holtzman,S.G. Sensitization and tolerance to the discriminative stimulus effects of mu-opioid agonists. Psychopharmacology 1994; 114(--):601-610. >>> Naloxone HCl; Morphine sulfate; Meperidine HCl; Fentanyl citrate; Saline; SC; rat; 2ML1; 7 days; controls received sham pumps; tolerance.

P2408 Paronis,C.A., Holtzman,S.G. Development of tolerance to the analgesic activity of mu agonists after continuous infusion of morphine, meperidine or fentanyl in rats. J.Pharmacol.Exp.Ther. 1992; 262(-1-):1-9. >>> Morphine; Meperidine; Fentanyl; Saline; SC; rat; 2ML1; 1 week; tolerance.

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

17. Methadone

P7057 Leri,F., Tremblay,A., Sorge,R.E., Stewart,J. Methadone maintenance reduces heroin- and cocaine-induced relapse without affecting stress-induced relapse in a rodent model of poly-drug use. Neuropsychopharmacology 2004; 29(-7-):1312-1320. >>> Methadone HCL; Saline, physiological; SC; Rat; 2ML2; 2 weeks; Controls received mp w/ vehicle, or sham surgery; dose-response (Fig. 1); dependence.

P6850 Hou,Y.N., Yuri,T.A., Belcheva,M.M., Clark,A.L., Zahm,D.S., Coscia,C.J. Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling. DEVELOPMENTAL BRAIN RESEARCH 2004; 151(-1-2-):149-157. >>> Buprenorphine; naloxone; methadone; SC; Rat (pregnant); 2ML4; ; Controls received mp w/ water; dose-response (fig. 3); teratology.

P6729 Lewanowitsch,T., White,J.M., Irvine,R.J. Use of radiotelemetry to evaluate respiratory depression produced by chronic methadone administration. European Journal of Pharmacology 2004; 484(-2-3-):303-310. >>> Methadone, hydrochloride; Saline; SC; Rat; 2ML1; 4 days; Controls received mp w/ vehicle; tolerance; telemetry device used in IP cavity during SC infusion.

P5623 Holtzman,S.G. Discrimination of a single dose of morphine followed by naltrexone: Substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence. Journal of Pharmacology and Experimental Therapeutics 2003; 304(-3-):1033-1041. >>> Fentanyl; methadone; Saline; water, distilled; SC; Rat; 2ML2; 14 Days; Dependence.

P5301 Robinson,S.E., Wallace,M.J. Effect of perinatal buprenorphine exposure on development in the rat. J Pharmacol Exp.Ther 2001/8; 298(-2-):797-804. >>> Buprenorphine HCl; Methadone HCl; Water, sterile; SC; Rat (pregnant); 28-39 days; Controls received mp w/ vehicle; toxicology; teratology; some pumps replaced after 28 days.

P5008 Robinson,S.E., Wallace,M.J. Effect of perinatal buprenorphine exposure on development in the rat. Journal of Pharmacology and Experimental Therapeutics 2001; 298(--):797-804. >>> Buprenorphine; Methadone; Water; SC; rat (pregnant); rat (neonate); 14, 28 days; controls received mp w/ vehicle; dose-response (graphs p. 802); teratology; toxicology; dependence; 28-day pumps implanted in pregnant rats; 14-day pumps implanted in 10-day old rat pups..

P3775 Robinson,S.E., Maher,J.R., Wallace,M.J., Kunko,P.M. Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat. Neurotoxicol.Teratol. 1997; 19(-4-):295-303. >>> Methadone HCl; SC; rat (pregnant); 42 days; controls received mp w/sterile water; dependence; long-term study, pumps replaced after 4 weeks; teratology.

P3487 Zhou,Y., Spangler,R., Maggos,C.E., LaForge,K.S., Ho,A., Kreek,M.J. Steady-state methadone in rats does not change mRNA levels of corticotropin-releasing factor, its pituitary receptor or proopiomelanocortin. Eur.J.Pharmacol. 1996; 315(--):31-35. >>> Methadone; Saline; SC; rat; 2001; 7 days; controls received mp w/ saline; half-life of 70-90 minutes in rats (p. 32).

P3431 Robinson,S.E., Mo,Q., Maher,J.R., Wallace,M.J., Kunko,P.M. Perinatal exposure to methadone affects central cholinergic activity in the weanling rat. Drug Alcohol Depend. 1996; 41(--):119-126. >>> Methadone HCl; SC; rat; no duration posted; controls received pumps with sterile water; long-term study, pumps replaced after 28 days; teratology; dependence.

P3429 Kunko,P.M., Smith,J.A., Wallace,M.J., Maher,J.R., Saady,J.J., Robinson,S.E. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat. J.Pharmacol.Exp.Ther. 1996; 277(-3-):1344-1351. >>> Methadone HCl; Water, sterile; SC; rat (pregnant); no duration posted; controls received vehicle infusion; controls received mp w/vehicle; long-term study, pumps replaced after 28 days; teratology; dependence.

P3075 Zmitrovich,A.C., Brake,S.C., Liu,P.-Y.R., Hamowy,A.S., Hutchings,D.E. Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age. Neurotoxicol.Teratol. 1994; 16(-3-):251-255. >>> Methadone HCl; Water, sterile; SC; rat (pregnant); no duration posted; controls received mp with water or no treatment; toxicology; teratology.

R0096 Hutchings,D.E., Zmitrovich,A., Church,S., Malowany,D. Methadone during pregnancy: the search for a valid animal model. Ann.Ist.Super.Sanita 1993; 29(-3-):439-444. >>> Methadone; no duration posted; methadone half-life (p.441); substance abuse.

P2879 Robinson,S.E., Guo,H., Spencer,R.F. Prenatal exposure to methadone delays the development of striatal cholinergic neurons. Dev.Brain Research 1993; 76(--):239-248. >>> Methadone HCl; SC; rat (pregnant); no duration posted; controls received mp with water; teratology.

P2319 Hutchings,D.E., Zmitrovich,A.C., Brake,S.C., Church,S.H., Malowany,D. Prenatal administration of methadone in the rat increases offspring acoustic startle amplitude at age 3 weeks. Neurotoxicol.Teratol. 1993; 15(--):157-164. >>> Methadone HCl; Saline; Water; SC; rat (pregnant); no duration posted; controls received mp w/ saline; functionality of mp verified by weighing; teratology; "...minipump affords a pharmacologically appropriate animal model of methadone maintenance during pregnancy and one of particular relevance to its therapeutic use during pregnancy (p. 162).

P2196 Darmani,N.A., Schnoll,S.H., Pandey,U., Martin,B.R. Chronic prenatal methadone exposure alters central opioid u-receptor affinity in both fetal and maternal brain. Neurotoxicol.Teratol. 1992; 14(-4-):265-271. >>> Methadone HCl; Water; rat (pregnant); 7 days; dependence.

P2031 Hutchings,D.E., Zmitrovich,A., Brake,S.C., Malowany,D., Church,S., Nero,T.J. Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat. Neurotoxicol.Teratol. 1992; 14(--):65-71. >>> Methadone HCl; Water; IP; rat (pregnant); 2002; 14 days; teratology.

P2421 Robinson,S.E., Guo,H., McDowell,K.P., Pascua,J.R., Enters,E.K. Prenatal exposure to methadone affects central cholinergic neuronal activity in the weanling rat. Dev.Brain Research 1991; 64(--):183-188. >>> Methadone HCl; Water; SC; rat (pregnant); no duration posted; controls received mp w/ vehicle.

P2198 Darmani,N.A., Saady,J.J., Schnoll,S.H., Martin,B.R. Demonstration of physical dependence following chronic continuous methadone delivery via osmotic minipumps in pregnant rats. Neurotoxicol.Teratol. 1991; 13(-6-):627-630. >>> Methadone; Water; SC; rat (pregnant); 2ML2; 14 days; controls received mp w/vehicle; functionality of mp verified by plasma and tissue levels (p.629); no stress (see p.630); dependence.

P1953 Enters,E.K., Guo,H., Pandey,U., Ko,D., Robinson,S.E. The effect of prenatal methadone exposure on development and nociception during the early postnatal period of the rat. Neurotoxicol.Teratol. 1991; 13(--):161-166. >>> Methadone HCl; SC; rat (pregnant); no duration posted; teratology; dependence.

P1924 Darmani,N.A., Schnoll,S.H., Fuchs,B., Martin,B.R. Does chronic prenatal methadone exposure affect B-receptor subtypes in placental, fetal and maternal brain homogenates. Neurotoxicol.Teratol. 1991; 13(--):43-48. >>> Methadone HCl; Water; rat (pregnant); 2 weeks; teratology; dependence; paper incorrectly states that pumps held 2 ml and delivered 1 ul/hr.

P2394 Guo,H., Enters,E.K., McDowell,K.P., Robinson,S.E. The effect of prenatal exposure to methadone on neurotransmitters in neonatal rats. Dev.Brain Research 1990; 57(--):296-298. >>> Methadone HCl; Water; SC; rat (pregnant); no duration posted; controls received mp w/ water; teratology.

P1301 Seran,G.F., Sparber,S.B. Metabolism of methadone by chicken embryos prevents induction of chronic opioid-type dependence after a single injection: use of osmotic pumps for continuous infusion. Pharmacol.Biochem.Behav. 1988; 30(-2-):357-363. >>> Methadol, N-desmethyl-1-acetyl; Methadone; Radio-isotopes; 3H tracer; Propylene glycol; Saline; Water; in vitro; bird (chicken embryo); 2001; 7 days; pump delivered to chicken egg via catheter; pump extracorporeal; comparison of a single injection vs. mp infusion.

P0964 Wang,C., Pasulka,P., Perry,B., Pizzi,W.J., Schnoll,S.H. Effect of perinatal exposure to methadone on brain opioid and alpha2-adrenergic receptors. Neurobehav.Toxicol.Teratol. 1986; 8(--):399-402. >>> Methadone HCl; Water; SC; rat; 7 days; teratology.

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

18. Morphine 2000-2007

P8303 Zissen,M.H., Zhang,G., McKelvy,A., Propst,J.T., Kendig,J.J., Sweitzer,S.M. Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats. Neuroscience 2007; 144(-1-):247-262. >>> Morphine; Saline; SC; Rat (neonate); 1003D; 72 hours; Controls received mp w/ vehicle; dose-response (p. 250); comparison of acute or intermittently injections vs. mp; vs. pellet; good methods (p. 249); tolerance; post op. care (IP penicillin, fluid therapy); animal info (Sprague-Dawley); morphine withdrawal; behavioral testing.

P8037 Wu,G.J., Wen,Z.H., Chen,W.F., Chang,Y.C., Cherng,C.H., Wong,C.S. The effect of dexamethasone on spinal glutamine synthetase and glutamate dehydrogenase expression in morphine-tolerant rats. Anesthesia and Analgesia 2007; 104(-3-):726-730. >>> Morphine; dexamethasone; CSF/CNS (intrathecal); Rat; 2001; 5 days; Animal info (male, Wistar, 350-370 grams).

P8011 Tai,Y.H., Wang,Y.H., Wang,J.J., Tao,P.L., Tung,C.S., Wong,C.S. Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats. Pain 2006; 124(-1-2-):77-86. >>> Amitriptyline; morphine; Saline; CSF/CNS (intrathecal); SC; Rat; 2001; 5 days; Tolerance; animal info (male, Wistar, 350-400 grams); behavioral study.

P8010 Suzuki,R., Porreca,F., Dickenson,A.H. Evidence for spinal dorsal horn hyperexcitability in rats following sustained morphine exposure. Neuroscience Letters 2006; 407(-2-):156-161. >>> Morphine; Saline; SC; 14 days; Controls received mp w/ vehicle.

P7934 Zissen,M.H., Zhang,G.H., Kendig,J.J., Sweitzer,S.M. Acute and chronic morphine alters formalin pain in neonatal rats. Neuroscience Letters 2006; 400(-1-2-):154-157. >>> Morphine; Saline; Rat (neonate); 1003D; 72 hours; Controls received mp w/ vehicle; post op. care (penicillin, ringer's solution); animal info (male and female Sprague-Dawley); Vetbond tissue used.

P7884 Jhamandas,K., Milne,B., Sutak,M., Gouarderes,C., Zajac,J.M., Yang,H.Y.T. Facilitation of spinal morphine analgesia in normal and morphine tolerant animals by neuropeptide SF and related peptides. Peptides 2006; 27(-5-):953-963. >>> Morphine sulfate; CSF/CNS (intrathecal); Rat; 2001; 6 days; Comparison of IT injections vs. mp; tolerance; animal info (male, Sprague-Dawley, 250-275g.).

P7789 Banach,T., Zurowski,D., Gil,K., Weilsbrodt,N.W., Rosenfeld,G., Thor,P.J. Peripheral mechanisms of intestinal dysmotility in the morphine tolerant and dependent rats. Journal of Physiology and Pharmacology 2006; 57(-1-):73-82. >>> Morphine; SC; Rat; 2001; 72 hours; Tolerance; dependence: animal info (male, Wistar, 200g.).

P7714 Juni,A., Klein,G., Kest,B. Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: Evidence for multiple diverse hyperalgesic systems. Brain Research 2006; 1070(-1-):35-44. >>> Morphine; morphine-3B-glucoronide; Saline; SC; Mice; 2001; 6,12,14,19 days; Controls received mp w/ vehicle; dose-response (fig. 1); pumps replaced; tolerance; animal info (adult, male, CD-1).

P7681 Colpaert,F.C., Deseure,K., Stinus,L., Adriaensen,H. High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning. Journal of Pharmacology and Experimental Therapeutics 2006; 316(-2-):892-899. >>> F13640; morphine, HCl; Saline; SC; Rat; 2ML2; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every two weeks; multiple pumps per animal (2); animal info (male, Sprague-Dawley, 220-240 g); during pump replacement a new incision was made about 1 cm away from the previous incision.

P7610 Feng,P., Rahim,R.T., Cowan,A., Liu-Chen,L.Y., Peng,X.H., Gaughan,J., Meissler,JJ Jr, Adler,M.W., Eisenstein,T.K. Effects of mu, kappa or delta opioids administered by pellet or pump on oral Salmonella infection and gastrointestinal transit. European Journal of Pharmacology 2006; 534(-1-3-):250-257. >>> Morphine sulfate; enkephalin analog DPDPE; U50,488H; deltorphin II, D-ala2-; Saline, pyrogen free; SC; Mice; 1003D; 48 hours; Controls received mp w/ vehicle; dose-response (fig 1); comparison of pellets vs. mp; immunology; animal info (female, 6 wk old); mp primed 4 hours in 37 C saline; "morphine pellet potently exacerbated oral salmonella infection, but morphine given by pump, at doses which were immunosuppresive had a substantially lesser effect (of infection)." (p. 251).

P7716 Prokai,L., Zharikova,A.D., Stevens,SM Jr. Effect of chronic morphine exposure on the synaptic plasma-membrane subproteome of rats: a quantitative protein profiling study based on isotope-coded affinity tags and liquid chromatography/mass spectrometry. JOURNAL OF MASS SPECTROMETRY 2005; 40(-2-):169-175. >>> Morphine sulfate; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; dependence; animal info (male, Sprague-Dawley, adult, 250-300g).

P7686 Alexander,M., Daniel,T., Chaudry,I.H., Schwacha,M.G. Opiate analgesics contribute to the development of post-injury immunosuppression. Journal of Surgical Research 2005; 129(-1-):161-168. >>> Morphine; Saline; SC; Mice; 1007D; 7 days; Animal info (C57BL/6, female, 20-25 g, 8-10 weeks old).

P7544 Daniels,D.J., Lenard,N.R., Etienne,C.L., Law,P.Y., Roerig,S.C., Portoghese,P.S. Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2005; 102(-52-):19208-19213. >>> Morphine; DN-20; MDAN-16; MDAN-17; MDAN-18; MDAN-19; MDAN-20; MDAN21; MA19; Saline, sterile; CSF/CNS; Mice; 1003D; 3 days; Controls received mp w/ vehicle; tolerance; dependance; cyanoacrylate adhesive; animal info (male, ICR, 25-30 g); mp primed in 37 C saline overnight; MDAN is mu-delta-agonist-antagonist series to opioid receptors of bivalent ligands that contain different length spacers (16-21 atoms) and pharmocophores derived from naltrindole; MA is mu-agonist monovalent control; DN is delta antagonist monovalent control.

P7465 Lenard,N.R., Roerig,S.C. Development of antinociceptive tolerance and physical dependence following morphine i.c.v. infusion in mice. European Journal of Pharmacology 2005; 527(-1-3-):71-76. >>> Morphine sulfate; Saline, sterile; CSF/CNS; Mice; 1003D; 3 days; Controls received mp w/ vehicle; comparison of sc pellets vs. mp; no stress (see pg. 73); tolerance; dependence; cyanoacrylate adhesive; post op. care (antibacterial ointment); animal info (male, 28-45 g); mp primed in sterile saline 37C overnight.

P7457 Lin,J.A., Lee,M.S., Wu,C.T., Yeh,C.C., Lin,S.L., Wen,Z.H., Wong,C.S. Attenuation of morphine tolerance by intrathecal gabapentin is associated with suppression of morphine-evoked excitatory amino acid release in the rat spinal cord. Brain Research 2005; 1054(-2-):167-173. >>> Morphine; gabapentin; Saline, normal; CSF/CNS (intrathecal); Rat; 2001; 5 days; Controls received mp w/ vehicle; comparison of acute IT infusions vs. mp; tolerance; animal info (male, Wistar, 400-450 g).

P7415 White,D.A., Hwang,A.L., Holtzman,S.G. Naltrexone-induced conditioned place aversion following a single dose of morphine in the rat. Pharmacology Biochemistry and Behavior 2005; 81(-3-):451-458. >>> Morphine; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; good methods p. 453; animal info (male, sprague dawley, 250-370 g).

P7414 Wen,Z.H., Wu,G.J., Chang,Y.C., Wang,J.J., Wong,C.S. Dexamethasone modulates the development of morphine tolerance and expression of glutamate transporters in rats. Neuroscience 2005; 133(-3-):807-817. >>> Dexamethasone; morphine; CSF/CNS (intrathecal, occipital); Rat; 2001; 5 days; Controls received mp w/ saline or dex; animal info (male, wistar, 400-500 g).

P7378 Tawfik,V.L., LaCroix-Fralish,M.L., Nutile-McMeneny,N., DeLeo,J.A. Transcriptional and translational regulation of glial activation by morphine in a rodent model of neuropathic pain. Journal of Pharmacology and Experimental Therapeutics 2005; 313(-3-):1239-1247. >>> Morphine; SC; CSF/CNS (intrathecal); Rat; 1007D; 2002; 2ML2; 3, 6, 14 days; Controls received mp w/ saline; dose-response (Fig. 1); comparison of SC mp vs. IT mp; tolerance; mp primed overhight in 37 degrees celsius saline, "a continuous adminstration protocol was used to prevent daily variations in plasma drug levels, which have been shown to enhance tolerance." (p. 1246).

P7241 Gu,G.B., Kondo,I., Hua,X.Y., Yaksh,T.L. Resting and evoked spinal substance P release during chronic intrathecal morphine infusion: Parallels with tolerance and dependence. Journal of Pharmacology and Experimental Therapeutics 2005; 314(-3-):1362-1369. >>> Morphine sulfate; saline, sterile physiological; CSF/CNS (intrathecal); Rat; 2001; 1, 6 days; Controls received mp w/ vehicle; tolerance; dependence.

P7185 Kim,S.Y., Chudapongse,N., Lee,S.M., Levin,M.C., Oh,J.T., Park,H.J., Ho,I.K. Proteomic analysis of phosphotyrosyl proteins in morphine-dependent rat brains. MOLECULAR BRAIN RESEARCH 2005; 133(-1-):58-70. >>> Morphine sulfate; Saline, sterile physiological; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; good methods p. 60; dependence; post op. care (sensorcaine, procaine penicillin G); mp primed overnight in 35 degrees celsius saline.

P6896 Fornai,F., Schlueter,O.M., Lenzi,P., Gesi,M., Ruffoli,R., Ferrucci,M., Lazzeri,G., Busceti,C.L., Pontarelli,F., Battaglia,G., Pellegrini,A., Nicoletti,F., Ruggieri,S., Paparelli,A., Suedhof,T.C. Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and alpha-synuclein. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2005; 102(-9-):3413-3418. >>> MPTP; L-dopa; apomorphine; IP; SC; Mice; 2004; 1-28 days; Controls received mp w/ saline; comparison of IP injections vs. mp; neurodegenerative (Parkinson's disease); L-dopa and apomorphine group had SC implanted pumps; route is unclear for the MPTP group; "Continuous MPTP infusions thus recreate a disease state that mimics human PD better than acute MPTP bolus injections." (p. 3417); MPTP group received IP pumps (2004 model), verified by e-mailing author.

P6895 Poonawala,T., Levay-Young,B.K., Hebbel,R.P., Gupta,K. Opioids heal ischemic wounds in the rat. Wound Repair and Regeneration 2005; 13(-2-):165-174. >>> Morphine; PBS; SC; Rat; 8 days; Controls received mp w/ vehicle; comparison of topical opioids and injections vs. mp; wound healing.

P7086 Al Amin,H.A., Atweh,S.F., Baki,S.A., Jabbur,S.J., Saade,N.E. Continuous perfusion with morphine of the orbitofrontal cortex reduces allodynia and hyperalgesia in a rat model for mononeuropathy. Neuroscience Letters 2004; 364(-1-):27-31. >>> Morphine sulfate; CSF/CNS (orbitofrontal cortex); Rat; 2002; 14 days; Controls received no nerve injury; functionality of mp verified by histological assessment of cannula tip placement.

P7082 Trujillo,K.A., Kubota,K.S., Warmoth,K.P. Continuous administration of opioids produces locomotor sensitization. Pharmacology Biochemistry and Behavior 2004; 79(-4-):661-669. >>> Morphine sulfate; fentanyl; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; comparison of pellets vs. mp; tolerance; mp primed overnight in saline at room temperature; pain; animal info (225-250 grams).

P7020 Stoller,D.C., Smith,F.L. Buprenorphine blocks withdrawal in morphine-dependent rat pups. PEDIATRIC ANESTHESIA 2004; 14(-8-):642-649. >>> Morphine sulphate; Water, distilled; SC; Rat (neonate); 1003D; 72 hours; Controls received mp w/ isotonic saline; dependence.

P7012 Yoburn,B.C., Purohit,V., Patel,K., Zhang,Q.Y. Opioid agonist and antagonist treatment differentially regulates immunoreactive mu-opioid receptors and dynamin-2 in vivo. European Journal of Pharmacology 2004; 498(-1-3-):87-96. >>> Naloxone; etorphine hcl; morphine sulfate; Saline, normal; SC; Mice; 2001; 7 days; Controls received inert, placebo pellets or saline injections; comparison of SC injections vs. pellets vs. mp; tolerance; "Intermittent naloxone and etorphine treatment did not regulate u-opioid receptor or dynamin-2, despite the fact that the total amount of drug administered was the same as continuous treatment." (pg. 94); animal info (m, 22-30 grams).

P7011 Wang,C.H., Lee,T.H., Tsai,Y.J., Liu,J.K., Chen,Y.J., Yang,L.C., Lu,C.Y. Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats1. Acta Pharmacologica Sinica 2004; 25(-8-):1027-1030. >>> Roscovitine; morphine; DMSO; CSF/CNS (intrathecal); Rat; 2001; 5 days; Enzyme inhibitor (cyclin dependent kinase 5); tolerance.

P6990 Xu,G.P., Van Bockstaele,E., Reyes,B., Bethea,T., Valentino,R.J. Chronic morphine sensitizes the brain norepinephrine system to corticotropin-releasing factor and stress. Journal of Neuroscience 2004; 24(-38-):8193-8197. >>> Morphine sulfate; Saline, sterile; CSF/CNS; Rat; 2001; 7 days; Controls received mp w/ vehicle; dependence.

P6574 Wen,Z.H., Chang,Y.C., Cherng,C.H., Wang,J.J., Tao,P.L., Wong,C.S. Increasing of intrathecal CSF excitatory amino acids concentration following morphine challenge in morphine-tolerant rats. Brain Research 2004; 995(-2-):253-259. >>> Morphine; MK-801; CSF/CNS (intrathecal); Rat; 2001; 5 days; Controls received mp w/ saline; tolerance.

P6468 Lane,D.A., Tortorici,V., Morgan,M.M. Behavioral and electrophysiological evidence for tolerance to continuous morphine administration into the ventrolateral periaqueductal gray. Neuroscience 2004; 125(-1-):63-69. >>> Morphine sulfate; CSF/CNS (periaqueductal gray); Rat; 2-4 days; Controls received mp w/ saline; tolerance.

P6445 Supanz,S., Likar,R., Liebmann,P.M., Wintersteiger,R., Sittl,R., Sadjak,A. On the role of the kidneys in the pathogenesis of edema formation during permanent morphine application. ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH 2004; 54(-5-):259-264. >>> Morphine; Saline; SC; Rat; 2ML1; ; Controls received mp w/ vehicle; dose-response (p.262); "our studies indicate that continuous subcutaneous delivery using mini-pumps is particularly useful since it closely mimics the intravenous route or pump administration by which opioids are continuously administered to humans." p.262.

P6401 Bailey,A., Davis,L., Lesscher,H.M.B., Kelly,M.D.W., Ledent,C., Hourani,S.M.O., Kitchen,I. Enhanced morphine withdrawal and mu-opioid receptor G-protein coupling in A2A adenosine receptor knockout in mice. Journal of Neurochemistry 2004; 88(-4-):827-834. >>> Morphine; Saline; SC; Mice (knockout); 1007D; 7 days; Controls received mp w/ vehicle; dependence.

P6223 Dunbar,S.A., Karamian,I.G. Cross-tolerance between spinal neostigmine and morphine in the rat. British Journal of Anaesthesia 2003; 91(-3-):427-429. >>> Morphine sulfate; neostigmine methysulfate; CSF/CNS (intrathecal); Rat; 2001; 6 days; Controls received mp w/ saline; tolerance.

P6099 Roy,S., Balasubramanian,S., Wang,J.H., Chandrashekhar,Y., Charboneau,R., Barke,R. Morphine inhibits VEGF expression in myocardial ischemia. Surgery 2003; 134(-2-):336-344. >>> Morphine; Saline; IV (jugular); Rat; 2001; 1 week; Controls received mp w/ vehicle; ischemia (cardiac).

P5962 Fan,L.W., Tien,L.T., Tanaka,S., Ma,T., Chudapongse,N., Sinchaisuk,S., Rockhold,R.W., Ho,I.K. Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol. Neuroscience 2003; 121(-4-):1063-1074. >>> Butorphanol; morphine; Saline, sterile; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; dependence; post op. care (penicillin, 0.5% sensorcaine in wound site); guide cannula with stylet was used; dental cement used to adhere cannula to skull; protective aluminuim cap was placed around the cannula; tygon tubing was used; solutions were filter sterilized during filling of the pumps; brain diagram (p. 1066).

P5902 Deseure,K., Koek,W., Adriaensen,H., Colpaert,F.C. Continuous administration of the 5-hydroxytryptamine 1A agonist (3-ch loro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]-methadone (F 13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-2-):505-514. >>> F13640; F13714; morphine; bacioten; Saline; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; Post Op. Care (aerosol bandage applied to protect against bacterial contamination); F13640 is a novel analgesic&5-HT1A receptor agonist; behavorial study; F13640, F13714&morphine were infused in one pump; bacioten infused in two pumps due to limited solubility; contro.

P5893 Kalinichev,M., Holtzman,S.G. Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: Similarities and differences between acute and chronic dependence. Journal of Pharmacology and Experimental Therapeutics 2003; 304(-2-):603-609. >>> Morphine; Saline; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; comparison of acute injections vs. chronic mp; tolerance; dependence; multiple pumps per animal used (2).

P5865 Vonhof,S., Gudka,B.D., Siren,A.L. Tolerance and dependence following chronic intracerebroventricular infusions of Tyr-D-Arg(2)-Phe-Sar(4) (TAPS). European Journal of Pharmacology 2003; 459(-1-):41-48. >>> Morphine sulfate; Enkephalin analog DAMGO; Dermorphin-derived tetrapeptide (TAPS); CSF, artifical; CSF/CNS; Rat; 2001; 6 days; Controls received mp w/ vehicle; comparison of bolus injections vs. chronic mp; pumps replaced on day 4 to achieve 6 days due to dead space in catheter; ALZET brain infusion kit used; tolerance; dependence; peptides; second hole with guide cannula&stylet used for bolus injections; (ALZET) cannula placement confimed by fast green dye&the guide cannula confirmed by methylene blue; TAPS is a potent mu-opioid receptor agonist.

P5860 Schmitt,T.K., Mousa,S.A., Brack,A., Schmidt,D.K., Rittner,H.L., Welte,M., Schafer,M., Stein,C. Modulation of peripheral endogenous opioid analgesia by central afferent blockade. Anesthesiology 2003; 98(-1-):195-202. >>> Morphine, HCL; Saline; CSF/CNS (intrathecal); Rat; 2ML1; 6, 48 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; analgesia; 4 day recovery; correct placement of I.T. catheter was tested by an injection of 10 ul lidocaine.

P5717 Lin,C.R., Yang,L.C., You,H.L., Lee,C.T., Tai,M.H., Tan,P.H., Lin,M.W., Cheng,J.T. Antinociceptive potentiation and attenuation of tolerance by intrathecal electric stimulation in rats. Anesthesia and Analgesia 2003; 96(-6-):1711-1716. >>> Morphine; Saline; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; stress/adverse reaction: (see pg. 1713) 10 animals excluded from study, 5 due to implantation failure, 3 due to pump failure, 2 due to infection; dependence; PE-10 joined to PE-20, which was joined to PE-60.

P5658 Ibuki,T., Marsala,M., Masuyama,T., Yaksh,T.L. Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats. British Journal of Pharmacology 2003; 138(-4-):689-697. >>> Morphine; CSF/CNS (intrathecal); Rat; 2002; 3 days; Controls received mp w/ saline; tolerance..

P6585 Colpaert,F.C., Tarayre,J.P., Koek,W., Pauwels,P.J., Bardin,L., Xu,X.J., Wiesenfeld-Hallin,Z., Cosi,C., Carilla-Durand,E., Assie,M.B., Vacher,B. Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology 2002; 43(-6-):945-958. >>> F13640; morphine HCL; imipramine HCl; ketamine HCl; gabapentin; Water, double distilled; SC; Rat; 2ML2; 14 days; Controls received mp w/ saline; dose-response (fig. 3); comparison of IP&SC injections vs. mp; tolerance; dependence; "Continuous F 13640 infusion uniquely produced profound analgesia in this model of severe, chronic pain." (p. 955).

P6208 Fan,L.W., Tanaka,S., Tien,L.T., Ma,T.G., Rockhold,R.W., Ho,I.K. Withdrawal from dependence upon butorphanol uniquely increases kappa1-opioid receptor binding in the rat brain. Brain Research Bulletin 2002; 58(-2-):149-160. >>> Butorphanol tartrate; morphine; Saline, sterile physiological; CSF/CNS; Rat; 2001; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual drug volume; good methods (p. 150); dependence; post op. care (sensorcaine, procaine penicillin G); guide cannula&stylet used; dental cement secured cannula.

P6183 Zhu,H., Ho,I.K., Kramer,R.E, Baker,R.C., Rockhold,R.W. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine. International Journal of Molecular Sciences 2002; 3(--):1073-1081. >>> Morphine sulfate; CSF/CNS; Rat; 2001; 3 days; Dependence; guide cannula with stylet used to maintain cannula patency; verified by presence of CSF in cannula.

P6140 Mao,J.R., Sung,B.K., Ji,R.R., Lim,G. Neuronal apoptosis associated with morphine tolerance: Evidence for an opioid-induced neurotoxic mechanism. Journal of Neuroscience 2002; 22(-17-):7650-7661. >>> Morphine; MK-801; zVAD-fmk; AC-DEVD-CHO; Saline; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; good methods p. 7651; enzyme inhibitor (pan caspase); tolerance; analgesic; AC-DEVD-CHO and zVAD-fmk are caspase inhibitors.

P5492 Gomes,B.A., Shen,J., Stafford,K., Patel,M., Yoburn,B.C. mu-opioid receptor down-regulation and tolerance are not equally dependent upon G-protein signaling. Pharmacology Biochemistry and Behavior 2002; 72(-1-2-):273-278. >>> Etorphine HCl; morphine sulfate; Saline; SC; Mice; 3 days; Tolerance.

P5483 Hua,X.Y., Moore,A., Malkmus,S., Murray,S.F., Dean,N., Yaksh,T.L., Butler,M. Inhibition of spinal protein kinase C alpha expression by an antisense oligonucleotide attenuates morphine infusion-induced tolerance. Neuroscience 2002; 113(-1-):99-107. >>> Morphine; Saline; CSF/CNS (intrathecal); Rat; 5 days; Tolerance; double lumen catheter used.

P5479 Sinchaisuk,S., Ho,I.K., Rockhold,R.W. Focal kappa-opioid receptor-mediated dependence and withdrawal in the nucleus paragigantocellularis. Pharmacology Biochemistry and Behavior 2002; 74(-1-):241-252. >>> Morphine sulfate; butorphanol tratrate; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ saline; dependence; minipumps were inserted 6-10 days after guide cannula implantation; stylet used.

P5341 Stoller,D.C., Thornton,S.R., Smith,F.L. Loss of antinociceptive efficacy in rat pups infused with morphine from osmotic minipumps. Pharmacology 2002; 66(-1-):11-18. >>> Morphine sulfate; Saline, isotonic; SC; Rat (neonate); 1003D; 72 hours; Controls received mp w/ saline; toxicology; teratology; tolerance; dependence; 6-day and 14-day old rat pups implanted; incision closed w/ vetbond tissue adhesive.

P5337 Slot,L.A.B., Tarayre,J.P., Koek,W., Ribet,J.P., Colpaert,F.C. Experimental conditions for the continuous subcutaneous infusion of four central analgesics in rats. Pharmacology Biochemistry and Behavior 2002; 72(-4-):943-951. >>> Morphine HCl; Ketamine HCl; Imipramine HCl; gabapentin; Water, distilled; SC; Rat; 2ML2; 2 weeks; Controls received mp w/ saline; no stress (see pg. 947); 14 day stability verified by HPLC on all agents; the site of pump placement was massaged daily to avoid tissue adherance; opioid and non-opioid analgesics; body weight gain information provided.

P5291 Battaglia,G., Busceti,C.L., Cuomo,L., Giorgi,F.S., Orzi,F., De Blasi,A., Nicoletti,F., Ruggieri,S., Fornai,F. Continuous subcutaneous infusion of apomorphine rescues nigro-striatal dopaminergic terminals following MPTP injection in mice. Neuropharmacology 2002; 42(-3-):367-373. >>> Apomorphine; Saline; SC; Mice; 28 days; Controls received mp w/ vehicle; comparison of sc bolus injections vs. mp; 20-day stability verified by HPLC (p.368); neurodegenerative (Parkinson's disease); "The neurorescue effect of continuous subcutaneous infusion of apomorphine is particularly promising from a clinical standpoint." (p.372).

P5183 Javelle,N., Berod,A., Renaud,B., Lambas-Senas,L. NO synthase inhibitors attenuate locus coeruleus catecholamine metabolism and behavior induced by morphine withdrawal. NeuroReport 2002; 13(-5-):725-728. >>> Morphine sulfate; SC; Rat; 2ML1; ; dependence.

P5153 Kalinichev,M., Easterling,K.W., Holtzman,S.G. Early neonatal experience of Long-Evans rats results in long-lasting changes in morphine tolerance and dependence. Psychopharmacology 2001/9; 157(-3-):305-312. >>> Morphine; SC; rat; 2ML1; 1 week; controls received mp w/ saline; tolerance; dependence.

P5000 Tokuyama,S., Zhu,H., Oh,S., Ho,I.K., Yamamoto,T. Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids. NEUROCHEMISTRY INTERNATIONAL 2001; 39(--):103-109. >>> Morphine; Butorphanol; Saline; CSF/CNS; rat; 2001; 3 days; controls received mp w/ vehicle; good methods (p. 104-105); dependence; opioid agonists; cannula placement assessed by the presence of CSF in the guide cannula; stylets used to maintain cannula patency during 1-week recovery period;.

P4966 Stafford,K., Gomes,A.B., Shen,J., Yoburn,B.C. Mu-opioid receptor downregulation contributes to opioid tolerance in vivo. Pharmacology Biochemistry and Behavior 2001; 69(--):233-237. >>> Etorphine hydrochloride; Morphine sulfate; Saline; SC; mice; 2001; 7 days; controls received placebo pellet; functionality of mp verified by analgesia "tail-flick" dose-response test; comparison of morphine pellets vs. mp; tolerance; receptor downregulation; animal info (male, swiss webster, 22-40 grams).

P4917 Chew,M., White,J.M., Somogyi,A.A., Bochner,F., Irvine,R.J. Precipitated withdrawal following codeine administration is dependent on CYP genotype. European Journal of Pharmacology 2001; 425(--):159-164. >>> Morphine tartrate; Codeine phosphate; Saline; SC; rat; 2ML1; 7 days; functionality of mp verified by plasma drug levels; dose response (graphs p. 161); dependence.

P4910 Houghton,A.K., Parsons,C.G., Headley,P.M. Mrz 2/579, a fast kinetic NMDA channel blocker, reduces the development of morphine tolerance in awake rats. Pain 2001; 91(--):201-207. >>> Morphine HCl; Mrz 2/579; Saline; SC; rat; 2ML1; 72 hours; controls received mp w/ vehicle; half-life (p. 202) Mrz 2/579 plasma of 140-180 minutes; Mrz 2/579 is an NMDA channel blocker (antagonist); one group received morphine alone, other group received multiple pumps per animal (2), one containing morphine, one containing Mrz 2/579;.

P4844 Kest,B., Palmese,C.A., Hopkins,E., Adler,M., Juni,A. Assessment of acute and chronic morphine dependence in male and female mice. Pharmacology Biochemistry and Behavior 2001; 70(--):149-156. >>> Morphine sulfate; Saline; SC; mice; 2001; 7 days; controls received mp w/ vehicle; dose response (graph p. 153); dependence; no stress: "Subcutaneously implanted pumps also minimizes possible contextual conditioning due to repeated handling, injection of drug, and drug effect, which can influence withdrawal behavior." p. 154.

P4800 Li,X., Angst,M.S., Clark,J.D. Opioid-induced hyperalgesia and incisional pain. Anesthesia and Analgesia 2001; 93(--):204-209. >>> Morphine sulfate; Naloxone;; Saline;; SC;; rat;; 2ML1;; 6 days;; Controls received mp w/ vehicle; tolerance; dependence;.

P4790 Vanderah,T.W., Suenaga,N.M.H., Ossipov,M.H., Malan,TP Jr, Lai,J., Porreca,F. Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance.. Journal of Neuroscience 2001; 21(-1-):279-286. >>> Morphine; Saline; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; comparison of pellets vs. mp; also used morphine pellets; pain.

P5535 Johnstone,L.E., Brown,C.H., Meeren,H.K., Vuijst,C.L., Brooks,P.J., Leng,G., Russell,J.A. Local morphine withdrawal increases c-fos gene, Fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells. J.Neurosci. 2000/2/1; 20(-3-):1272-1280. >>> Morphine sulfate; Ringer's solution; CSF/CNS; Rat; 2001; 2002; ; Controls received mp w/ vehicle; tolerance; dependence; increasing concentrations of morphine; pump filled w/ morphine at 50 ug/ul; catheter tubing contained 40 ul of 10 ug/ul morphine solution followed by 40 ul of 20 ug/ul of morphine solution.

P5245 Tokuyama,S., Ho,I.K., Yamamoto,T. A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats. Brain Res Bull. 2000/7/15; 52(-5-):363-369. >>> Morphine; Butorphanol; H7; Saline; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ vehicle; enzyme inhibitor; dependence; H7 is a protein kinase C inhibitor; tygon tubing used; one week recovery period; guide cannula with stylet used to ensure patency; concomitant infusion of H7 and opioids performed by mixing agents in the same pump.

P4755 Jang,C.-G., Rockhold,R.W., Ho,I.K. An autoradiographic study of [3H]AMPA receptor binding and in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits following morphine withdrawal in the rat brain.. Brain Research Bulletin 2000; 52(-3-):217-221. >>> Morphine;; Saline;; CSF/CNS;; rat;; 2001;; 3 days;; Controls received mp w/ vehicle; tolerance; dependence;.

P4723 Chen,X, Marrero,H.G, Murphy,R, Lin,Y.-J, Freedman,J.E. Altered gating of opiate receptor-modulated K+ channels on amygdala neurons of morphine-dependent rats.. PNAS 2000; 97(-26-):14692-14696. >>> Morphine;; Water;; SC;; rat;; 2001;; 6 days;; Controls received mp w/ vehicle; tolerance; dependence;.

P4674 Shen,J, Gomes,B, Gallagher,A, Stafford,K, Yoburn,B.C. Role of cAMP-dependent protein kinase (PKA) in opioid agonist-induced m-opioid receptor downregulation and tolerance in mice.. Synapse 2000; 38(--):322-327. >>> Etorphine; Morphine;; SC;; mice;; 2001;; 2, 3 days;; Controls received inert placebo pellet; opioid agonists; etorphine infused for 2 days; morphine infused for 3 days; morphine pellets also used in mp/morphine implanted mice;.

P4653 Dunbar,S.A., Karamov,I.G, Buerkle,H. The effect of spinal ibuprofen on opioid withdrawal in the rat.. Anesth.Analg. 2000; 91(--):417-422. >>> Morphine sulfate;; CSF/CNS (spinal cord, intrathecal);; rat;; 2001;; 5 days;; Controls received mp w/ saline; dependence; detailed description of catheter preparation and surgical implantation (pgs. 417-418)..

19. Nalbuphine

T0009 Kistler,P. Zur schmerzbekampfung im tierversuch: Eine studie zur wahl geeigneter analgetika fur die schmerzbekampfung bei versuchstieren. Dissertation, Universitat Bern, Zurich 1988; (--):-. >>> D16949; Flupirtine; Tramadol; Buprenorphine; Nalbuphine; SC; mice; rat; 2-7 weeks; German with English abstract (p. 7), pump cross-section and dimensions (pg. 94).

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

20. Naproxen

P1504 Chan,W.Y., Berezin,I., Daniel,E.E. Effects of inhibition of prostaglandin synthesis on uterine oxytocin receptor concentration and myometrial gap junction density in parturient rats. Biol.Reprod. 1988; 39(--):1117-1128. >>> Naproxen, sodium; Saline; SC; rat (pregnant); 2001; 3 days; no comment posted.

21. Normorphine

P0173 Schulz,R., Wuster,M. Are there sybtypes (isoreceptors) of multiple opiate receptors in the mouse vas deferens. Eur.J.Pharmacol. 1981; 76(--):61-66. >>> Endorphin, a-neo-; DsThr; Dynorphin; Enkephalin analog DADLE; FK-33824; MR-2034; MRZ; Normorphine; Sufentanil; Water; SC; mice; 2001; 6 days; peptides; MRZ is 5,9-dimethyl,2'S-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan, a kappa opioid agonist.

P0170 Schulz,R., Wuster,M., Rubini,P., Herz,A. Functional opiate receptors in the guinea-pig ileum: their differentiation by means of selective tolerance development. J.Pharmacol.Exp.Ther. 1981; 219(-2-):547-550. >>> DsThr; Enkephalin agonist DADL; Fentanyl; FK-33824; MR-2034; MRZ; Normorphine; Water; SC; guinea-pig; 2001; 6 days; peptides.

22. Oxymorphone

P4892 Gillingham,M.B., Clark,M.D., Dahly,E.M., Krugner-Higby,L.A., Ney,D.M. A comparison of two opioid analgesics for relief of visceral pain induced by intestinal resection in rats. CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE 2001; 40(-1-):21-26. >>> Oxymorphone HCl; IP; rat; 32 hours; functionality of mp verified by pain relief indicators - posture, physical condition, behavior; comparison of iv infusions vs mp; compared bolus iv infusion, continuous iv infusion, osmotic pump..

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

23. Pentazocine

P3459 Bergeron,R., de Montigny,C., Debonnel,G. Effect of short-term and long-term treatments with sigma ligands on the N-methyl-D-aspartate response in the CA(3) region of the rat dorsal hippocampus. Br.J.Pharmacol. 1997; 120(--):1351-1359. >>> Haloperidol; JO-1784; Pentazocine; DTG; SC; rat; 2-21 days; controls received mp w/saline; DTG is di(2-tolyl)guanidin.

P1911 Weissman,A.D., De Souza,E.B. Chronic treatment of rats with the specific sigma ligand D-pentazocine fails to modulate dopamine D2 and sigma binding in brain. Eur.J.Pharmacol. 1991; 195(--):163-165. >>> Pentazocine, d-; Saline; SC; rat; 2ML4; 4 weeks; no comment posted.

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

24. Propoxyphene

P0588 Schmidt,W.K., Tam,S.W., Shotzberger,G.S., Smith Jr,D.H., Clark,R., Vernier,V.G. Nalbuphine. Drug Alcohol Depend. 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; 3 days; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

25. Sodium Salicylate

P4829 Yuan,M, Konstantopoulos,N, Lee,J, Hansen,L, Li,Z.-W, Karin,M, Shoelson,S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 2001; 293(--):1673-1677. >>> Acetylsalicylic acid; Salicylate, sodium;; SC; Rat; mice; 2002; 2ML2; 3-4 weeks; Controls received mp w/ vehicle; 2ML2 used in rats, 2002 used in mice; acetylsalicylic acid also called aspirin: dose was 120 mg/kg/day; diabetes (type II).

P3550 Gordon,C.J. Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat. Pharmacol.Biochem.Behav. 1996; 55(-2-):185-194. >>> Scopolamine; Methylscopolamine nitrate; Salicylate, sodium; SC; rat; 2002; 10 days; temperatures were taken with radiotelemetry.

P1664 Bergman,K., Cekan,E., Slanina,P., Gabrielsson,J., Hellenas,K.-E. Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat. Toxicology 1990; 61(--):135-146. >>> Salicylate, sodium; Water; IV; rat; 2ML1; no duration posted; teratology.

T0005 Gabrielsson,J. Modeling of drugs in pregnancy: the application of pharmacokinetic principles and physiological flow models. Dissertation, Uppsala University, Sweden 1985; (--):-. >>> Salicylate, sodium; Saline; IV (jugular); rat (pregnant); 2ML1; 1 week; comparison of iv injec vs. mp infusion; advantages&disadvantages of mp pp. 56-57; dose-response data; stability of salicylic acid vs. aspirin p. 47.

P0826 Gabrielsson,J., Paalzow,L., Larsson,S., Blomquist,I. Constant rate of infusion - improvement of tests for teratogenicity and embryotoxicity. Life Sci. 1985; 37(-24-):2275-2282. >>> Salicylate, sodium; IV (jugular); rat (pregnant); 2ML1; 7 days; comparison of iv bolus injection vs. mp infusion; controls received mp; mp infusion during two periods of gestation; dose-response; teratology; embryotoxicity; study to determine effects on offspring.

26. Sufentanil

P4728 Diaz,A, Florez,J., Pazos,A, Hurle,M.A. Opioid tolerance and supersensitivity induce regional changes in the autoradiographic density of dihydropyridine-sensitive calcium channels in the rat central nervous system.. Pain 2000; 86(--):227-235. >>> Sufentanil citrate; Nimodipine;; Saline; Ethanol; Propylene glycol; Water;; SC;; rat;; 2001;; 7 days;; Controls received mp w/ vehicle; tolerance; Group 1 received vehicle alone, Group 2 received chronic sufentanil, Group 3 received sufentanil&nimodipine, Group 4 received nimodipine alone; Nimodipine is a CA2+ antagonist opioid; sufentanil citrate was diluted in saline; nimodipine was diluted in 10% ethanol / 20% propylene glycol / 70% water.

P4727 Diaz,A, Pazos,A, Florez,J., Hurle,M.A. Autoradiographic mapping of m-opioid receptors during opiate tolerance and supersensitivity in the rat central nervous system.. Nauyn-Schmiedeberg's Arch Pharmacol 2000; 362(--):101-109. >>> Sufentanil citrate; Nimodipine;; Saline; Ethanol; Propylene glycol; Water;; SC;; rat;; 2001;; 7 days;; Controls received mp w/ vehicle; tolerance; Group 1 received sufentanil, Group 2 received sufentanil&nimodipine, Group 3 received nimodipine, Group 4 received vehicle; Nimodipine is a Ca channel blocker; sufentanil was diluted in saline; nimodipine was diluted in 10% ethanol / 20% propylene glycol / 70% water;.

P3361 Garaulet,J.V., Laorden,M.L., Milanes,M.V. Effect of chronic administration of dihydropyridine Ca2+ channel ligands on sufentanil-induced tolerance to u- and k- opioid agonists in the guinea pig ileum myenteric plexus. Regul.Pept. 1996; 63(--):1-8. >>> Sufentanil; Nimodipine; Bay K 8644; Saline; SC; guinea-pig; 2001; 7 days; controls received mp w/saline; tolerance.

R0117 Stevens,C.W. Perspectives on opioid tolerance from basic research: behavioural studies after spinal administration in rodents. Cancer Surveys 1994; 21(--):25-47. >>> Morphine; DADLE; ST-91; Sufentanil; DAMGO; CSF/CNS (spinal cord, intrathecal); rat; 7 days; controls received mp w/ saline; cancer; peptides; tolerance; comprehensive review of mp infusion methods using y-catheter.

P4187 Garaulet,J.V., Laorden,M.L., Milanes,M.V. Cross-tolerance between mu- and kappa-opioid agonists in the guinea pig ileum myenteric plexus. J.Pharmacol.Exp.Ther. 1994; 269(-3-):993-999. >>> Sufentanil; Saline, sterile; SC; guinea-pig; 2001; 7 days; controls received mp w/vehicle; tolerance.

R0132 Yaksh,T.L. Tolerance: factors involved in changes in the dose-effect relationship with chronic drug exposure. In 'Towards a new pharmacotherapy of pain', A.I.Basbaum&J.-M.Besson (eds), John Wiley&Sons Ltd 1991; (--):-. >>> Morphine; Sufentanil; Enkephalin; Saline; IV; CSF/CNS (intrathecal); CSF/CNS; rat; 7 days; controls received mp w/vehicle; dose-response (p. 163); tolerance; pain; reference of mp pump study on pp. 162-164.

P2081 Sosnowski,M., Yaksh,T.L. Differential cross-tolerance between intrathecal morphine and sufentanil in the rat. Anesthesiology 1990; 73(--):1141-1147. >>> Morphine sulfate; Sufentanil citrate; Saline; CSF/CNS (spinal cord, intrathecal); rat; 2001; 7 days; dose-response; tolerance; PE10 heat fused to PE60; externalized loop of catheter permitted cessation of infusion without pump removal.

P1612 Stevens,C.W., Yaksh,T.L. Magnitude of opioid dependence after continuous intrathecal infusion of mu and delta-selective opioids in the rat. Eur.J.Pharmacol. 1989; 166(--):467-472. >>> Sufentanil citrate; Enkephalin analog DADLE; Enkephalin analog DAMGO; Morphine; Saline; CSF/CNS (spinal cord, intrathecal); rat; 2001; 7 days; tissue infusion; dose-response; peptides; tolerance, dependence.

P1560 Stevens,C., Yaksh,T.L. Potency of infused spinal antinociceptive agents is inversely related to magnitude of tolerance after continuous infusion. J.Pharmacol.Exp.Ther. 1989; 250(-1-):1-8. >>> Enkephalin analog DADLE; Enkephalin analog DAMGO; Enkephalin analog ST-91; Morphine sulfate; Sufentanil citrate; Saline; CSF/CNS (spinal cord, intrathecal); rat; 2001; 7 days; mp connected to Y-catheter; dose-response; peptides.

P1529 Ayesta,F.J., Florez,J. Tolerance to respiratory actions of sufentanil: functional tolerance and route-dependent differential tolerance. J.Pharmacol.Exp.Ther. 1989; 250(-1-):371-378. >>> Sufentanil citrate;; Saline; SC; rat; 2001; 7 days; controls received mp w/ saline; comparison of sc, iv&icv injections; tolerance; agent mu opioid receptor agonist; pumps left in longer than 7 days; "possibility that the minipump implanting process could influence the results was eliminated . . . no difference . . . in nonimplanted and implanted rats." (p. 372).

P1273 Stevens,C.W., Yaksh,T.L. Time course characteristics of tolerance development to continuously infused antinociceptive agents in rats spinal cord. J.Pharmacol.Exp.Ther. 1989; 251(-1-):216-223. >>> Enkephalin analog ST-91; Enkephalin analog DADLE; Enkephalin analog DAMGO; Morphine; Sufentanil; Saline; CSF/CNS (spinal cord, intrathecal); rat; 2001; 7 days; no comment posted.

P1299 Millan,M.J., Morris,B.J. Long-term blockade of u-opioid receptors suggests a role in control of ingestive behaviour, body weight and core temperature in the rat. Brain Research 1988; 450(--):247-258. >>> Bremazocine; MR-2266; MR-2267; Naloxone; Sufentanil; DMSO; HCl; Sodium hydroxide; Propylene glycol; Water; SC; rat; 2001; 2ML1; 3, 6, 7 days; mp malfunction -- pump plugged at 4 days due to propylene glycol; water was vehicle for naloxone; propylene glycol, HCl, NaOH was vehicle for MR-2200; pump replaced at 3 days.

P1206 Fujinaga,M., Mazze,R.I., Jackson,E.C., Baden,J.M. Reproductive and teratogenic effects of sufentanil and alfentanil in sprague-dawley rats. Anesth.Analg. 1988; 67(--):166-169. >>> Alfentanil; Sufentanil; Saline; SC; rat (pregnant); 2ML2; 14 days; controls received mp w/ saline; dose-response (text); 3 doses of sufentanil infused; agents infused separately; author states 'in terms of experimental design, the cost of using sc implanted osmotic minipumps is small'; teratology.

P0173 Schulz,R., Wuster,M. Are there sybtypes (isoreceptors) of multiple opiate receptors in the mouse vas deferens. Eur.J.Pharmacol. 1981; 76(--):61-66. >>> Endorphin, a-neo-; DsThr; Dynorphin; Enkephalin analog DADLE; FK-33824; MR-2034; MRZ; Normorphine; Sufentanil; Water; SC; mice; 2001; 6 days; peptides; MRZ is 5,9-dimethyl,2'S-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan, a kappa opioid agonist.

P0127 Schulz,R., Wuster,M., Herz,A. Differentiation of opiate receptors in the brain by the selective development of tolerance. Pharmacol.Biochem.Behav. 1981; 14(--):75-79. >>> Enkephalin analog DADLE; Sufentanil; CSF/CNS; SC; rat; 2001; 7-8 days; comparison of chronic vs. acute infusion of DADL; DADL infused ivt, SUF infused sc; peptides.

P0119 Wuster,M., Schulz,R., Herz,A. The direction of opioid agonists towards u-, g- and E-receptors in the vas deferens of the mouse and rat. Life Sci. 1980; 27(--):163-170. >>> Enkephalin analog DADLE; Sufentanil; SC; mice; 2001; 6 days; peptides.

P0113 Schulz,R., Wuster,M., Krenss,H., Herz,A. Lack of cross-tolerance on multiple opiate receptors in the mouse vas deferens. Mol.Pharmacol. 1980; 18(-3-):395-401. >>> Enkephalin analog DADLE; Etorphine; Sufentanil; SC; mice; 2001; 1, 3, or 6 days; separate&simultaneous infusion of agents; peptides.

P0102 Wuster,M., Schulz,R., Herz,A. Highly specific opiate receptors for dynorphin-(1-13) in the mouse vas deferens. Eur.J.Pharmacol. 1980; 62(-2/3-):235-236. >>> Enkephalin analog DADLE; Sufentanil; SC; mice; 2001; 6 days; simultaneous infusion of agents; peptides.

P0101 Schulz,R., Wuster,M., Krenss,H., Herz,A. Selective development of tolerance without dependence in multiple opiate receptors of mouse vas deferens. Nature 1980; 285(-5762-):242-243. >>> Enkephalin analog DADLE; Sufentanil; SC; mice; 1701; 6 days; peptides.

27. Tramadol

P4849 Tsai,Y.C., Won,S.J. Effects of tramadol on T lymphocyte proliferation and natural killer cell activity in rats with sciatic constriction injury. Pain 2001; 92(--):63-69. >>> Tramadol; Saline; SC; rat; 2ML1; 7 days; controls received mp w/ vehicle; comparison of sc injections vs. mp; immunology; multiple pumps per animal (2) used in high-dose groups; nociception; tramadol is a centrally acting analgesic..

P4947 Tsai,Y.C., Sung,Y.H., Chang,P.J., Kang,F.C., Chu,K.S. Tramadol relieves thermal hyperalgesia in rats with chronic constriction injury of the sciatic nerve. FUNDAMENTAL&CLINICAL PHARMACOLOGY 2000; 14(--):335-340. >>> Tramadol; Saline; SC; rat; 2ML1; 7 days; controls received mp w/ vehicle; functionality of mp verified by paw withdrawal latency (analgesia index); dose-response (graph p. 337); comparison of sc injection vs. mp; analgesia..

T0009 Kistler,P. Zur schmerzbekampfung im tierversuch: Eine studie zur wahl geeigneter analgetika fur die schmerzbekampfung bei versuchstieren. Dissertation, Universitat Bern, Zurich 1988; (--):-. >>> D16949; Flupirtine; Tramadol; Buprenorphine; Nalbuphine; SC; mice; rat; 2-7 weeks; German with English abstract (p. 7), pump cross-section and dimensions (pg. 94).

28. Zomepirac

S0199 Cowan,A., Tortella,F.C., Gmerek,D.E. EEG and behavioral studies with zomepirac sodium in rats. Pain 1981; 11(-1-):194-. >>> Zomepirac, sodium; Water; CSF/CNS; SC; rat; 2001; no duration posted; 7 days icv, 3 days sc.

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