References on Tolerance and Dependence Research Using ALZET® Osmotic Pumps
Q0694 Quillinan,N., Lau,E.K., Virk,M., von Zastrow,M., Williams,J.T. Recovery from mu-Opioid Receptor Desensitization after Chronic Treatment with Morphine and Methadone. Journal of Neuroscience 2011; 31(-12-):4434-4443. >>> Morphine; methadone; Water; SC; Rat; 2ML1; 2001; 6 days; Controls received mp w/ vehicle; tolerance; animal info (adult (150-250 g, male, Sprague Dawley).
Q0735 Raehal,K.M., Bohn,L.M. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011; 60(-1-):58-65. >>> Morphine; methadone; fentanyl; oxycodone; Water, sterile, distilled; SC; Mice; 7 days; Animal info (male, WT, barr2-KO); dependence; wound clips used.
Q0651 Shioda,N., Beppu,H., Fukuda,T., Li,E., Kitajima,I., Fukunaga,K. Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in the ATRX Mutant Mouse Brain. Journal of Neuroscience 2011; 31(-1-):346-358. >>> KN-93; Krebs-Ringer HEPES; CSF/CNS; Mice; 1004; 2 weeks; Controls received mp w/ vehicle; animal info (ATRX-delta E2, adult, 12 wks old, male); enzyme inhibitor (Calcium/Calmodulin-Dependent Protein Kinase II, CaMKII).
Q0005 Boettger,M.K., Weber,K., Gajda,M., Braeuer,R., Schaible,H.G. Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis. BRAIN BEHAVIOR AND IMMUNITY 2010; 24(-3-):474-485. >>> Ketamine, Morphine; Saline; CSF/CNS (intrathecal); Rat; 2ML4; 21 days; Controls received mp w/ vehicle; tolerance; ALZET brain infusion kit used; half-life pg 477 (2.5 hrs in CSF (ketamine); 2.1 hrs (morphine)); animal info (Female, Lewis, 6-8 wks old, 160-180 g); dorsal laminectomy; behavioral testing (pain related behavior).
Q0016 Hill,K.G., Sable,H.J.K., Ferraro,FM III, Kiefer,S.W. Chronic Naltrexone Treatment and Ethanol Responsivity in Outbred Rats. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 2010; 34(-2-):272-279. >>> Naltrexone HCl; Saline, physiological; SC; Rat; 2ML4; 2 weeks; Controls received mp w/vehicle; dependence; animal info (male, Long-Evans, 250 g); dose-response (fig .1).
Q0746 Horvath,R.J., Romero-Sandoval,E.A., De Leo,J.A. Inhibition of microglial P2X(4) receptors attenuates morphine tolerance, Iba1, GFAP andμ opioid receptor protein expression while enhancing perivascular microglial ED2. Pain 2010; 150(-3-):401-413. >>> Morphine sulfate; naloxone; SC; Rat; 2ML1; 1, 4, 7 days; Controls received mp w/ saline; animal info (male, Sprague-Dawley, 175-200 g); one pump contained morphine plus naloxone; "All morphine pumps were filled with 0.833 mg/kg/hr morphine to deliver the equivalent of twice daily 10 mg/kg injections over the course of 24 h" pg 402; tolerance.
P9940 Juni,A., Cai,M.Y., Stankova,M., Waxman,A.R., Arout,C., Klein,G., Dahan,A., Hruby,V.J., Mogil,J.S., Kest,B. Sex-specific Mediation of Opioid-induced Hyperalgesia by the Melanocortin-1 Receptor. Anesthesiology 2010; 112(-1-):181-188. >>> Morphine; Saline; SC; Mice; 2001; 7 days; Animal info (naive, adult, CD-1, b6, e/e); "Osmotic pumps provide continuous infusion for 7 days, thereby preventing hyperalgesia associated with withdrawal in morphine-dependent subjects that can potentially confound experiments in which chronic morphine treatment is accomplished via repeated acute injections." pg. 182.
Q0031 Shirafuji,S., Liu,J.Y., Okamura,N., Hamada,K., Fujimiya,T. QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats With Acute Ethanol Withdrawal. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 2010; 34(-2-):223-230. >>> Carvedilol; Polyethylene glycol; water, distilled; IP; Rat; 2ML1; 7 days; Controls received mp w/vehicle; dependence; cardiovascular; no stress (see pg. 225); animal info (male, Wistar, 7 weeks old).
Q0033 Slotkin,T.A., Ryde,I.T., Seidler,F.J. Additive and synergistic effects of fetal nicotine and dexamethasone exposure on cholinergic synaptic function in adolescence and adulthood: Implications for the adverse consequences of maternal smoking and pharmacotherapy of preterm delivery. Brain Research Bulletin 2010; 81(--):552-560. >>> Nicotine bitartrate; Water, bacteriostatic; SC; Rat (pregnant); 2002; 21 days; Controls received mp w/ saline (veh plus sodium bitartrate); teratology; dependence; no stress (see pg. 554); animal info (female, Sprague-Dawley, 232 g); incision closed with wound clips.
Q0032 Slotkin,T.A., Seidler,F.J. Mimicking maternal smoking and pharmacotherapy of preterm labor: Interactions of fetal nicotine and dexamethasone on serotonin and dopamine synaptic function in adolescence and adulthood. Brain Research Bulletin 2010; 82(-1-2-):124-134. >>> Nicotine bitartrate; Water, bacteriostatic; SC; Rat (pregnant); 2002; 21 days; Controls received mp w/vehicle w/ sodium bitartrate); teratology; dependence; animal info (female, Sprague-Dawley, agent given through PN4); incision closed with wound clips.
Q0764 Tumati,S., Roeske,W.R., Largent-Milnes,T., Wang,R., Vanderah,T.W., Varga,E.V. Sustained morphine-mediated pain sensitization and antinociceptive tolerance are blocked by intrathecal treatment with Raf-1-selective siRNA. British Journal of Pharmacology 2010; 161(-1-):51-64. >>> Morphine; SC; Rat; 7 days; Controls received mp w/ saline; animal info (male, Sprague Dawley, adult, 200-225 g); behavioral testing (Mechanical allodynia, Antinociceptive tolerance).
R0282 Werner,U., Haschke,G., Herling,A.W., Kramer,W. Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes. REGULATORY PEPTIDES 2010; 164(-2-3-):58-64. >>> Lixisenatide; Rat; 12 weeks; Controls received mp w/ saline; animal info (prediabetic, obese, ZDF, 8 wks old); long-term study; obesity; Review, see Werner U, Gerlach M, Hofmann M, Herling AW. Treatment of obese Zucker diabetic fatty rats with novel GLP-1 receptor agonist AVE0010 improves oral glucose tolerance and glycaemic control without risk of hypoglycaemia [Abstract]. Diabetologia 2006;49(Suppl 1):398-9..
P9333 Almela,P., Milanes,M.V., Laorden,M.L. Tyrosine hydroxylase phosphorylation after naloxone-induced morphine withdrawal in the left ventricle. Basic Research In Cardiology 2009; 104(-4-):366-376. >>> HA-1004; Water, sterile; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (protein kinase); dependence; animal info (male, Sprague Dawley, 220-240 g.); HA-1004 is a protein kinase selective inhibitor; pumps primed for 5 hours.
Q0460 Almela,P., Atucha,N.M., Milanes,M.V., Laorden,M.L. Cross-Talk between Protein Kinase A and Mitogen-Activated Protein Kinases Signalling in the Adaptive Changes Observed during Morphine Withdrawal in the Heart. Journal of Pharmacology and Experimental Therapeutics 2009; 330(-3-):771-782. >>> HA-1004; calphostin C; Water; DMSO; SC; Rat; 2001; 7 days; Animal info (male, Sprague Dawley, 220-240 g); dependence; enzyme inhibitor (PKA, PKC); 0.6% DMSO used.
P9713 Canis,M., Mack,B., Gires,O., Maurer,M.H., Kuschinsky,W., Duembgen,L., Duelli,R. Increased densities of monocarboxylate transport protein MCT1 after chronic administration of nicotine in rat brain. NEUROSCIENCE RESEARCH 2009; 64(-4-):429-435. >>> Nicotine; SC; Rat; 2001; 1 week; Controls received mp w/saline; dependence; animal info (adult, Sprague Dawley, 250-350 g).
P9400 Coen,K.M., Adamson,K.L., Corrigall,W.A. Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement. Psychopharmacology 2009; 201(-4-):557-568. >>> Nicotine bitartrate; Saline; SC; Rat; 2002; 10-14 days; Controls received sham device; dependence; animal info (male, Long-Evans, 300-350 g.).
P9483 Galeote,L., Berrendero,F., Bura,S.A., Zimmer,A., Maldonado,R. Prodynorphin gene disruption increases the sensitivity to nicotine self-administration in mice. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 2009; 12(-5-):615-625. >>> Nicotine hydrogen tartrate salt; SC; Mice; 2001; 6 days; Controls received mp w/ saline; functionality of mp verified by residual volume; dependence; animal info (male, C57BL/6, wt, prodynorphin KO) dose (~ 25 mg/kg/d).
P9238 Grilli,M., Pittaluga,A., Merlo-Pich,E., Marchi,M. NMDA-mediated modulation of dopamine release is modified in rat prefrontal cortex and nucleus accumbens after chronic nicotine treatment. Journal of Neurochemistry 2009; 108(-2-):408-416. >>> Nicotine bitartrate; Saline; Rat; 2ML2; 14, 21, 28 days; Controls received mp w/ vehicle; pumps replaced after 14 days; dependence; animal info (male, Sprague Dawley, 200-250 g.).
P9714 Hamilton,K.R., Berger,S.S., Perry,M.E., Grunberg,N.E. Behavioral effects of nicotine withdrawal in adult male and female rats. Pharmacology Biochemistry and Behavior 2009; 92(-1-):51-59. >>> Nicotine bitartrate; SC; Rat; 2ML2; 7 days; Controls received mp w/saline; dependence; animal info (Sprague Dawley, male, female).
P9740 Jackson,K.J., Damaj,M.I. L-Type Calcium Channels and Calcium/Calmodulin-Dependent Kinase II Differentially Mediate Behaviors Associated with Nicotine Withdrawal in Mice. Journal of Pharmacology and Experimental Therapeutics 2009; 330(-1-):152-161. >>> Nicotine; Saline; Mice; 2002; 2004; 14, 28 days; Controls received mp w/vehicle; dependence; animal info (male, C57BL/6J).
Q0761 Jackson,K.J., Walters,C.L., Miles,M.F., Martin,B.R., Damaj,M.M. Characterization of pharmacological and behavioral differences to nicotine in C57B1/6 and DBA/2 mice. Neuropharmacology 2009; 57(-4-):347-355. >>> Nicotine; Saline, physiological; SC; Mice; 2002; 2004; 14 days; Controls received mp w/ saline; animal info (male, B6, D2, 20-25 g); wound clips used; "the nicotine dose used for chronic studies corresponds to approximately 2 mg/kg/h, which yields plasma levels of 0.1 uM, a dose within the plasma range of human smokers"; tolerance; withdrawal.
P9748 Klein,G., Rossi,G.C., Waxman,A.R., Arout,C., Juni,A., Inturrisi,C.E., Kest,B. The contribution of MOR-1 exons 1-4 to morphine and heroin analgesia and dependence. Neuroscience Letters 2009; 457(-3-):115-119. >>> Heroin hydrochloride; morphine sulfate; Saline; SC; Mice; 2001; ; Controls received mp w/vehicle; dependence; animal info (adult, male, CD-1).
Q0665 Madia,P.A., Dighe,S.V., Sirohi,S., Walker,E.A., Yoburn,B.C. Dosing protocol and analgesic efficacy determine opioid tolerance in the mouse. Psychopharmacology 2009; 207(-3-):413-422. >>> Etorphine; oxycodone; hydrocodone; methadone; Saline; DMSO; SC; Mice; 2001; 7 days; Controls received placebo pellets wrapped in nylon mesh; animal info (Male, Swiss Webster, 23-30 g); tolerance; comparison of SC injections vs mp; "Higher doses of hydrocodone, oxycodone, and methadone could not be infused due to solubility issues." pg 415; 20% DMSO used; "infusion with hydrocodone or methadone produced greater tolerance than acute or intermittent treatment" pg 417.
P9595 Marcinkiewcz,C.A., Prado,M.M., Isaac,S.K., Marshall,A., Rylkova,D., Bruijnzeel,A.W. Corticotropin-Releasing Factor Within the Central Nucleus of the Amygdala and the Nucleus Accumbens Shell Mediates the Negative Affective State of Nicotine Withdrawal in Rats. Neuropsychopharmacology 2009; 34(-7-):1743-1752. >>> Nicotine hydrogen tartrate; Saline; SC; Rat; 2ML4; ; Controls received mp w/vehicle; dependence; animal info (male, Wistar, 250-300).
Q0388 Raehal,K.M., Schmid,C.L., Medvedev,I.O., Gainetdinov,R.R., Premont,R.T., Bohn,L.M. Morphine-induced physiological and behavioral responses in mice lacking G protein-coupled receptor kinase 6. Drug and Alcohol Dependence 2009; 104(-3-):187-196. >>> Morphine; Water, distilled, sterile; SC; Mice; 2001; 7 days; Animal info (WT, GRK6-KO, 25-35 g); dependence.
P9710 Reti,I.M., Han,S., Miskimon,M., Rosen,J.B., Baraban,J.M. Nicotine and Delta9-Tetrahydrocannabinol Withdrawal Induce Narp in the, Central Nucleus of the Amygdala. Synapse 2009; 63(-3-):252-255. >>> Nicotine; SC; Rat; 7 days; Controls received mp w/saline or made nicotine dependent on day 7; dependence; animal info (male, 175-250 g).
P9594 Sirohi,S., Dighe,S.V., Madia,P.A., Yoburn,B.C. The Relative Potency of Inverse Opioid Agonists and a Neutral Opioid Antagonist in Precipitated Withdrawal and Antagonism of Analgesia and Toxicity. Journal of Pharmacology and Experimental Therapeutics 2009; 330(-2-):513-519. >>> Fentanyl; SC; Mice; 2001; 72 hours; Dependence; animal info (Swiss-Webster, 25-33g).
P9631 Slotkin,T.A., Seidler,F.J. Nicotine Exposure in Adolescence Alters the Response of Serotonin Systems to Nicotine Administered Subsequently in Adulthood. Developmental Neuroscience 2009; 31(-1-2-):58-70. >>> Nicotine bitartrate; Water, bacteriostatic; SC; Rat; 1002; 2ML2; 17 days; Controls received mp w/vehicle, dependence; animal info (PD30, PD90).
P9647 Tan,H.B., Bishop,S.F., Lauzon,N.M., Sun,N.L., Laviolette,S.R. Chronic nicotine exposure switches the functional role of mesolimbic dopamine transmission in the processing of nicotine's rewarding and aversive effects. Neuropharmacology 2009; 56(-4-):741-751. >>> Nicotine; Saline; SC; Rat; 2002; 7-14 days; Controls received mp w/vehicle; dependence; animal info (male, SD, 300-350g).
P9601 Trigo,J.M., Zimmer,A., Maldonado,R. Nicotine anxiogenic and rewarding effects are decreased in mice lacking beta-endorphin. Neuropharmacology 2009; 56(-8-):1147-1153. >>> Nicotine; SC; Mice; 2001; ; Controls received mp w/saline; dependence; animal info (8-12 wks old, lacking beta endorphin).
Q0789 Upadhya,M.A., Dandekar,M.P., Kokare,D.M., Singru,P.S., Subhedar,N.K. Involvement of neuropeptide Y in the acute, chronic and withdrawal responses of morphine in nociception in neuropathic rats: Behavioral and neuroanatomical correlates. Neuropeptides 2009; 43(-4-):303-314. >>> Morphine; CSF/CNS; Rat; 2001; 8 days; Animal info (adult, male, Sprague-Dawley, 230-250 g); tolerance; behavioral testing (thermal paw withdrawal test); guide cannula used.
Q0272 van Dorp,E.L.A., Kest,B., Kowalczyk,W.J., Morariu,A.M., Waxman,A.R., Arout,C.A., Dahan,A., Sarton,E.Y. Morphine-6 beta-glucuronide Rapidly increases Pain Sensitivity Independently of Opioid Receptor Activity in Mice and Humans. Anesthesiology 2009; 110(-6-):1356-1363. >>> Morphine-6 beta-glucuronide; MK-801; Saline; SC; Mice; 2001; ; Animal info (adult, male, CD-1, TrKO, B6129F1); "Osmotic pumps afford continuous opioid infusions and control for hyperalgesia associated with withdrawal in opioid-dependent subjects that potentially confounds experiments in which chronic opioid treatment is accomplished via repeated acute injections." pg 1357.
P9767 Zhang,Q., Chen,C., Lue,J.G., Xie,M.J., Pan,D.J., Luo,X., Yu,Z.Y., Dong,Q., Wang,W. Cell Cycle Inhibition Attenuates Microglial Proliferation and Production of IL-1-beta, MIP-1-alpha, and NO After Focal Cerebral Ischemia in the Rat. Glia 2009; 57(-8-):908-920. >>> Roscovitine; DMSO; saline; CSF/CNS; Rat; 2001; ; Controls received mp w/vehicle; functionality of mp verified by "weighing the cassette before placement and after the experiment" pg. 909; enzyme inhibitor (cyclin dependant kinase); ALZET brain infusion kit used; ischemia (cerebral); animal info (adult, male, Sprague Dawley, 220-270 g); 0.2% DMSO used; MCAO.
P9397 Chiodo,K.A., Laeck,C.M., Roberts,D.C.S. Cocaine self-administration reinforced on a progressive ratio schedule decreases with continuous D-amphetamine treatment in rats. Psychopharmacology 2008; 200(-4-):465-473. >>> Amphetamine sulfate, D-; Saline; SC; Rat; 2001; 7, 14 days; Controls received mp w/ vehicle; pump replaced after 7 days; no stress (see pg. 470, 472); tolerance; animal info (male, Sprague Dawley, 350 g.) Behavioral testing (cocaine self-administration, food-reinforced responding); "the present dose delivered via mini-pump is not debilitating or overtly toxic." (p. 472).
R0247 Fernstrom,J.D., Choi,S. The development of tolerance to drugs that suppress food intake. PHARMACOLOGY&THERAPEUTICS 2008; 117(-1-):105-122. >>> Fenfluramine; leptin; melanotan II; CSF, artificial; PBS; SC; CSF/CNS; Rat; 8 weeks; 7, 28 days; Controls received mp w/ vehicle; dose-response (fig. 5); pumps replaced; tolerance; peptides; animal info (male, obese); endocrinology; review, see p. 108-110.
P9157 Goicoechea,C., Sanchez,E., Cano,C., Jagerovic,N., Martin,M.I. Analgesic activity and pharmacological characterization of N-[1-phenylpyrazol-3-yl]-N-[1-(2-phenethyl)-4-piperidyl] propenamide, a new opioid agonist acting peripherally. European Journal of Pharmacology 2008; 595(-1-3-):22-29. >>> Fentanyl; IQMF-4; SC; Mice; 2001; 7 days; Controls received mp w/ saline; tolerance; animal info (male, CD1, 25-30 g.); IQMF-4 also known as N-[1-phenylpyrazol-3-yl]-N-[1-(2-phenethyl)-4-piperidyl] propenamide, is a fentanyl analog; behavioral testing (nociceptive response).
P9231 Gravius,A., Dekundy,A., Nagel,J., More,L., Pietraszek,M., Danysz,W. Investigation on tolerance development to subchronic blockade of mGluR5 in models of learning, anxiety, and levodopa-induced dyskinesia in rats. Journal of Neural Transmission 2008; 115(-12-):1609-1619. >>> MTEP; Tween 80; water; SC; Rat; 2ML1; 4, 7 days; Controls received mp w/ vehicle; tolerance; animal info (male, Sprague Dawley, 6-OHDA lesions, 220-250 g.); neurodegenerative (Parkinson's Disease); 1% Tween 80; 3-[(2-methyl-1, 3-thiazol-4-4yl) ethynyl] pyridine; behavioral testing (radial maze task, contextual fear conditioning, anxiety, freezing behavior, abnormal involuntary movements).
P8884 Gulick,D., Gould,T.J. Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment. Psychopharmacology 2008; 196(-3-):483-495. >>> Nicotine; Saline; SC; Mice; 1002; 12-14 days; Controls received mp w/ vehicle; tolerance; animal info (male, C57BL/6J, 8-12 wks old, 20-30g.).
P8855 Haugan,F., Rygh,L.J., Tjolsen,A. Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiologica Scandinavica 2008; 52(-5-):681-687. >>> Morphine; ketamine; SC; Rat; 2ML1; 7 days; Controls received mp w/ saline or no treatment; no stress (see pg. 683); tolerance; animal info (female, Sprague Dawley, 210-320); "No behavioral differences could be observed between groups, suggesting that the animals were not suffering significant distress due to the implantations + treatment." (p. 683); pain.
P8860 Jain,R., Mukherjee,K., Mohan,D. Effects of nitric oxide synthase inhibitors in attenuating nicotine withdrawal in rats. Pharmacology Biochemistry and Behavior 2008; 88(-4-):473-480. >>> Nicotine; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; dependence; animal info (adult, male, Wistar, albino, 60-90 days old, 150-175g.); "Before implantation, each pump was primed for 4h in physiological saline." pg 474.
P9485 Johnson,P.M., Hollander,J.A., Kenny,P.J. Decreased brain reward function during nicotine withdrawal in C57BL6 mice: Evidence from intracranial self-stimulation (ICSS) studies. Pharmacology Biochemistry and Behavior 2008; 90(-3-):409-415. >>> Nicotine hydrogen tartrate; Saline, physiological; SC; Mice; 2004; 13 days; Controls received mp w/ vehicle; comparison of SC injections vs. mp; dependence; post op. care (bacitracin ointment); animal info (male, C57BL/6, 6 wks old); behavioral testing (intracranial self stimulation threshold, brain reward function).
P9312 Jonkman,S., Risbrough,V.B., Geyer,M.A., Markou,A. Spontaneous nicotine withdrawal potentiates the effects of stress in rats. Neuropsychopharmacology 2008; 33(-9-):2131-2138. >>> Nicotine hydrogen tartrate; Saline, physiological; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; dependence; animal info (male, Wistar); behavioral testing (light-enhanced startle test).
P8848 Klein,G., Juni,A., Arout,C.A., Waxman,A.R., Inturrisi,C.E., Kest,B. Acute and chronic heroin dependence in mice: Contribution of opioid and excitatory amino acid receptors. European Journal of Pharmacology 2008; 586(-1-3-):179-188. >>> MK-801; LY293558; Saline, physiological; SC; Mice; 2001; ; Controls received vehicle; comparison of SC injections vs. mp; dependence; animal info (male, CD-1, adult); "only MK-801 infusion was effective in reducing the subsequent withdrawal jumping." (p. 186); "We observed that LY293558 delivery by continuous infusion-but not acute bolus dose injection-prior to acute heroin injection reduced naloxone-precipitated withdrawal jumping" (p. 186).
P9162 Kumar,P., Sunkaraneni,S., Sirohi,S., Dighe,S.V., Walker,E.A., Yoburn,B.C. Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation. European Journal of Pharmacology 2008; 597(-1-3-):39-45. >>> Hydromorphone; Saline; SC; Mice; 2001; 7 days; Controls received inert placebo pellet; tolerance; animal info (male, Swiss Webster, 22-30 g.); "There was substantially more tolerance with infusion treatment compared to injection treatment." pg. 43.
P9249 Laviolette,S.R., Lauzon,N.M., Bishop,S.F., Sun,N.L., Tan,H.B. Dopamine signaling through D1-like versus D2-like receptors in the nucleus accumbens core versus shell differentially modulates nicotine reward sensitivity. Journal of Neuroscience 2008; 28(-32-):8025-8033. >>> Nicotine hydrogen tartrate salt; Saline, physiological; NaOH; SC; Rat; 2002; 14 days; Controls received mp w/ vehicle; dependence; animal info (male, Sprague Dawley, 300-350 g.); behavioral testing (place conditioning).
P9308 Liu,J., Pan,H., Gold,M.S., Derendorf,H., Bruijnzeel,A.W. Effects of fentanyl dose and exposure duration on the affective and somatic signs of fentanyl withdrawal in rats. Neuropharmacology 2008; 55(-5-):812-818. >>> Fentanyl citrate; Saline, physiological; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; functionality of mp verified by plasma fentanyl levels; dose-responses (fig. 1); dependence; animal info (male, Wistar, 300-350 g.).
P9215 Merritt,L.L., Martin,B.R., Walters,C., Lichtman,A.H., Damaj,M.I. The endogenous cannabinoid system modulates nicotine reward and dependence. Journal of Pharmacology and Experimental Therapeutics 2008; 326(-2-):483-492. >>> Nicotine hydrogen tartrate salt; Saline; SC; Mice; 1007D; 2004; 7, 14 days; Controls received mp w/ vehicle; dependence; animal info (C57BL/6, wt, CB1KO, FAAH KO, male, female); behavioral testing (elevated plus maze, tail-flick test, plantar stimulator test, locomotor activity, place aversion test).
P9434 Paterson,N.E., Balfour,D.J.K., Markou,A. Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats. NICOTINE&TOBACCO RESEARCH 2008; 10(-6-):995-1008. >>> Bupropion HCl; Saline; SC; Rat; 2ML2; 14 days; Dose-response (fig 4); dependence; post op. care (antibacterial lotion); animal info (male, Wistar, 300-350 g.); "minipumps were used in the present study to deliver two bupripion doses... with the aim of establishing constantly high bupropion levels that may mitigate species differences in pharmacokinetics." (p. 1006).
P8892 Paterson,N.E., Semenova,S., Markou,A. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat. Psychopharmacology 2008; 198(-3-):351-362. >>> Desipramine; nicotine; Saline; water; SC; Rat; 2ML1; 2ML2; 2ML4; 7, 14, 28 days; pumps replaced; dependence; animal info (male, Wistar, 300-350g.); post op. care ("antibacterial preparation"); comparison of IP injections vs. SC mp; "The results of the present study indicated that chronic, but not acute, DMI treatment attenuated the anhedonic and somatic components of nicotine withdrawal and that chronic DMI treatment significantly decreased nicotineand food-maintained responding." pg. 358.
P9302 Rylkova,D., Boissoneault,J., Isaac,S., Prado,M., Shah,H.P., Bruijnzeel,A.W. Effects of NPY and the specific Y1 receptor agonist [D-His26]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. Neuropeptides 2008; 42(-3-):215-227. >>> Nicotine hydrogen tartrate; Saline; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; dependence; animal info (male, Wistar, 250-300 g.); behavioral testing (brain reward threshold, somatic withdrawal signs).
P8863 Shram,M.J., Siu,E.C.K., Li,Z.X., Tyndale,R.F., Le,A.D. Interactions between age and the aversive effects of nicotine withdrawal under mecamylamine-precipitated and spontaneous conditions in male Wistar rats. Psychopharmacology 2008; 198(-2-):181-190. >>> Nicotine; Saline; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; dependence; animal info (adolescent, adult, Wistar).
P9445 Sirohi,S., Dighe,S.V., Walker,E.A., Yoburn,B.C. The analgesic efficacy of fentanyl: Relationship to tolerance and mu-opioid receptor regulation. Pharmacology Biochemistry and Behavior 2008; 91(-1-):115-120. >>> Fentanyl hydrochloride; Saline; SC; Mice; 7 days; Controls received placebo pellets; dose-response (fig. 3); comparison of SC injections vs. mp; tolerance; animal info (male, Swiss Webster, 23-35 g.).
P9271 Steiner,A.A., Oliveira,D.L., Roberts,J.L., Petersen,S.R., Romanovsky,A.A. Nicotine administration and withdrawal affect survival in systemic inflammation models. Journal of Applied Physiology 2008; 105(-4-):1028-1034. >>> Nicotine bitartrate; Saline; SC; Mice; 1007D; 2002; 18 days; Controls received mp w/vehicle; pumps replaced after 13 days; dependence; animal info (male, C57BL/6, 25-35 g.).
P9454 Thomsen,M., Fink-Jensen,A., Woldbye,D.P.D., Woertwein,G., Sager,T.N., Holm,R., Pepe,L.M., Caine,S.B. Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats. Psychopharmacology 2008; 201(-1-):43-53. >>> Aripiprazole; Cyclodextrin, hydroxypropyl-b-; methylsulfonic acid; NaOH; SC; Rat; 2ML1; 5 days; Controls received mp w/ lowest dose which had no effect; dose-response (fig. 2); half-life (p. 46) 2 hours in rats, 60 hours in humans; tolerance; dependence; multiple pumps per animal (2); animal info (male, Sprague Dawley, 9 wks old, 400-500 g.); behavioral testing (cocaine self-administration); 20% cyclodextrin used.
P9455 Torres,O.V., Tejeda,H.A., Natividad,L.A., O'Dell,L.E. Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development. Pharmacology Biochemistry and Behavior 2008; 90(-4-):658-663. >>> Nicotine hydrogen tartrate; Saline, physiological; SC; Rat; 2ML2; 14 days; Dose-response (fig. 3); comparison of SC injections vs. mp; dependence; animal info (male, Wistar, adolescent, 28 days old); behavioral testing (conditioned place preference).
P9181 Van Vliet,E.A., Van Schaik,R., Edelbroek,P.M., da Silva,F.H.L., Wadman,W.J., Gorter,J.A. Development of tolerance to levetiracetam in rats with chronic epilepsy. Epilepsia 2008; 49(-7-):1151-1159. >>> Levetiracetam; Water, distilled; SC; Rat; 2ML1; 2 weeks; Functionality of mp verified; pumps replaced after 1 week; tolerance; animal info (male, Sprague Dawley, adult, 500-700 g.); "flow rate of each pump was verified after removal and corresponded to the range given by the manufacturer indicating that all minipumps functioned properly." pg. 1156.
P8755 Wen,Z.H., Wu,G.J., Hsu,L.C., Chen,W.F., Chen,J.Y., Shui,H.A., Chou,A.K., Wong,C.S. N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and associated glial fibrillary acid protein up-regulation: a proteomic approach. Acta Anaesthesiologica Scandinavica 2008; 52(-4-):499-508. >>> Morphine; MK-801; CSF/CNS (intrathecal); Rat; 2001; 5 days; Controls received mp w/ saline; tolerance; animal info (male, Wistar, 350-375g); NMDA receptor antagonist.
P8249 Almela,P., Cerezo,M., Gonzalez-Cuello,A., Milanes,M.V., Laorden,M.L. Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2007; 374(-4-):293-303. >>> HA-1004; Water, sterile; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (protein kinase A); cardiovascular; tolerance; dependence; animal info (male, Sprague-Dawley, 220-240g).
P8668 Almon,R.R., DuBois,D.C., Yao,Z.L., Hoffman,E.P., Ghimbovschi,S., Jusko,W.J. Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. PHYSIOLOGICAL GENOMICS 2007; 30(-3-):282-299. >>> Methylprednisolone; Saline; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; functionality of mp verified by MPL plasma levels via HPLC; replacement therapy (adrenalectomy); dose-response (fig. 7, p. 287); comparison of injections vs. mp; stress/adverse reaction: (see pg. 296) muscle atrophy; tolerance; animal info (male, Wistar, 339g); "By 6 h, MPL concentrations reach a stable steady state that is maintained throughout the 7-day infusion period. In contrast, single MPL doses... result in drug concentrations that dissipate in a biexponential fashion and fall below the level of dection by 7 h." p. 288.
P8373 Britton,A.F., Vann,R.E., Robinson,S.E. Perinatal nicotine exposure eliminates peak in nicotinic acetylcholine receptor response in adolescent rats. Journal of Pharmacology and Experimental Therapeutics 2007; 320(-2-):871-876. >>> Nicotine hydrogen tartrate, L-; Saline, physiological; SC; Rat (pregnant); 2ML4; ; Controls received mp w/ vehicle; no stress (see pg. 872-3); dependence; animal info (female, Sprague-Dawley, gestation day 7, >70 days old).
P8251 Bruijnzeel,A.W., Zislis,G., Wilson,C., Gold,M.S. Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 2007; 32(-4-):955-963. >>> Nicotine hydrogen tartrate; Saline, sterile; SC; Rat; 2ML2; 2ML4; 14, 28 days; Controls received mp w/ vehicle; dependence; animal info (male, Wistar, 250-300g.).
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).
P8510 Djalilian,H.R., Caicedo,E., Lessan,K., Grami,V., Le,C.T., Spellman,S.R., Pambuccian,S., Hall,W.A., Low,W.C., Ondrey,F.G. Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the treatment of upper aerodigestive squamous cell carcinoma in rats. CANCER IMMUNOLOGY IMMUNOTHERAPY 2007; 56(-8-):1207-1214. >>> Granulocyte-macrophage colony stimulating factor, murine; interleukin-12; PBS; SC; Rat; 28 days; Controls received mp w/ vehicle; dose-response (fig 1); no stress (see pg. 1209); cancer (upper aerodigestive tract carcinoma); peptides; animal info (Fisher 344, 125-150 g); good methods; "This latter method (mp) has several advantages. First, the use of minipumps obviates the cumbersome need to transfect tumor cells and completely characterize their cytokine repertoires. Second, it allows for independent and rigorous control over the kinetics of administration of cytokine and antigen dosages. Third, it may generate les controversy than those techniques requiring "gene therapy" IRB approval." (p. 1213)..
P9065 Dunbar,S.A., Karamian,I., Zhang,H.H. Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat. EUROPEAN JOURNAL OF PAIN 2007; 11(-1-):1-6. >>> Morphine sulfate; naloxone hydrochloride; ketorlac; SC; CSF/CNS (intrathecal); Rat; 2001; 4, 7 days; Controls received mp w/ saline; tolerance; animal info (adult, male, Sprague Dawley, 350 g.).
P8671 George,O., Ghozland,S., Azar,M.R., Cottone,P., Zorrilla,E.P., Parsons,L.H., O'Dell,L.E., Richardson,H.N., Koob,G.F. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-43-):17198-17203. >>> Nicotine; Saline; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; dependence; animal info (adult, male, Wistar, 280-330g).
P8806 Kalange,A.S., Kokare,D.M., Singru,P.S., Upadhya,M.A., Chopde,C.T., Subhedar,N.K. Central administration of selective melanocortin 4 receptor antagonist HS014 prevents morphine tolerance and withdrawal hyperalgesia. Brain Research 2007; 1181(--):10-20. >>> Morphine; CSF, artificial; NaOH; water, distilled; CSF/CNS; Rat; 2001; 7, 8 days; Controls received mp w/ vehicle; tolerance; dependence; animal info (male, Sprague Dawley, 220-260g.); cannula placement confimed with India ink.
P8673 Leri,F., Sorge,R.E., Cummins,E., Woehrling,D., Pfaus,J.G., Stewart,J. High-dose methadone maintenance in rats: Effects on cocaine self-administration and behavioral side effects. Neuropsychopharmacology 2007; 32(-11-):2290-2300. >>> Methadone HCl; SC; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; good methods p. 2291; dependence; animal info (male, Sprague-Dawley, Long Evans).
P8048 Liechti,M.E., Markou,A. Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats. European Journal of Pharmacology 2007; 554(-2-3-):164-174. >>> Nicotine; Saline; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; dependence; animal info (male, Wistar, 300-350 grams).
P9378 Lorentzon,M., Raamunddal,T., Bollano,E., Soussi,B., Waagstein,F., Omerovic,E. Vivo effects of myocardial creatine depletion on left ventricular function, morphology, and energy metabolism - Consequences in acute myocardial infarction. JOURNAL OF CARDIAC FAILURE 2007; 13(-3-):230-237. >>> Guanidinopropionic acid, beta-; Saline; SC; Rat; 2ML4; 4 weeks; Controls received mp w/ vehicle; no stress (see pg. 231, 233); animal info (male, Sprague Dawley, 6 wks old, 200 g., MI); ischemia (cardiac); "No local adverse skin reaction in the area of implanted osmotic minipumps was observed in the BGP group suggesting good tolerance of this novel BGP application route." (p. 233).
P8707 Nashmi,R., Xiao,C., Deshpande,P., McKinney,S., Grady,S.R., Whiteaker,P., Huang,Q., Clure-Begley,T., Lindstrom,J.M., Labarca,C., Collins,A.C., Marks,M.J., Lester,H.A. Chronic nicotine cell specifically upregulates functional alpha4* nicotinic receptors: Basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path. Journal of Neuroscience 2007; 27(-31-):8202-8218. >>> Nicotine hydrogen tartrate; SC; Mice; 2002; 10 days; Controls received mp w/ saline; tolerance; animal info (Hom alpha4YFP, 2-3 months old).
P8415 O'Dell,L.E., Torres,O.V., Natividad,L.A., Tejeda,H.A. Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats. NEUROTOXICOLOGY AND TERATOLOGY 2007; 29(-1-):17-22. >>> Nicotine base; Saline; SC; Rat; 2001; 2ML2; 14, 21 days; Controls received mp w/ vehicle; pumps replaced after 7 days; dependence; animal info (male, Wistar; 21, 27-42, 60-75 days old).
P8672 Popp,E., Schneider,A., Vogel,P., Teschendorf,P., Boettiger,B.W. Time course of the hypothermic response to continuously administered neurotensin. Neuropeptides 2007; 41(-5-):349-354. >>> Neurotensin; Saline; CSF/CNS; Rat; 1003D; ; Controls received mp w/ vehicle; dose-response (pg 351, fig. 1); comparison of SC injections vs. mp; ALZET brain infusion kit 2 used; tolerance; peptides; animal info (Wistar-Han, male, 300-350g); "Diffusion of neurotensin into the pump was avoided by a drop of sesame oil" p. 350; "Complete surgery took about 20 min" p. 350; neurotensin is a tridecapeptide.
P8436 Rabbani,Z.N., Batinic-Haberle,I., Anscher,M.S., Huang,J., Day,B.J., Alexander,E., Dewhirst,M.W., Vujaskovic,Z. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 2007; 67(-2-):573-580. >>> AEOL 10150; SC; Rat; 2002; 10 weeks; 8 days; Controls received mp w/ vehicle; functionality of mp verified by plasma AEOL 10150 concentrations; dose-response (fig. 4); long-term study; pumps replaced every 2 weeks; half-life (p. 574), short; cancer; animal info (female, Fisher-344, 150-170 grams); "Osmotic mini-pumps provided consistent and dose-dependent delivery of AEOL 10150," "a continuous availability of antioxidant via osmotic infusion pumps throughout the study." (p. 575).
P8664 Salas,R., Main,A., Gangitano,D., De Biasi,M. Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the alpha-7 nicotinic acetylcholine receptor subunit. Neuropharmacology 2007; 53(-7-):863-869. >>> Nicotine tartrate; Saline; SC; Mice; 1002; 13 days; Controls received mp w/ vehicle; tolerance; animal info (male, female, C57BL/6, 2-5 months).
P8434 Samaha,A.N., Seeman,P., Stewart,J., Rajabi,H., Kapur,S. "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. Journal of Neuroscience 2007; 27(-11-):2979-2986. >>> Haloperidol; olanzapine; Acetic acid, glacial; water; NaOH; SC; Rat; 2ML2; 2,12,13 days; Controls received mp w/ vehicle; dose-response (fig. 4); comparison of SC injections vs. mp; half-life (p. 2985), 24 hours in humans, 1.4 hours in rats; tolerance; animal info (male, Sprague-Dawley, 225-250 grams); "Animal studies that use a mode of drug administration that more closely mimics clinical antipsychotic treatment (i.e., relatively continuous treatment) might be more informative about the true effects of these drugs in humans." (p. 2985).
P8448 Slotkin,T.A., Seidler,F.J. A unique role for striatal serotonergic systems in the withdrawal from adolescent nicotine administration. NEUROTOXICOLOGY AND TERATOLOGY 2007; 29(-1-):10-16. >>> Nicotine bitartrate; sodium bitartrate; Water, bacteriostatic; SC; Rat; 1007D; 1002; 2ML2; 7,17 days; Controls received mp w/ vehicle and sodium bitartrate; comparison of sc injections vs. mp; no stress (see pg. 13-14); dependence; animal info (Sprague-Dawley, 30 days old, male, 90 days old).
P8494 Stoller,D.C., Sim-Selley,L.J., Smith,F.L. Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine-tolerant infant rats. Brain Research 2007; 1142(--):28-36. >>> Morphine; SC; Rat (neonate); 1003D; 72 hours; Controls received mp w/ vehicle; tolerance; post op. care (10% povidone iodine swab); animal info (P14, 30 g); Vetbond tissue adhesive used to close incision.
P8396 Wenzel,P., Hink,U., Elze,M., Schuppan,S., Schaeuble,K., Schildknecht,S., Ho,K.K., Weiner,H., Bachschmid,M., Muenzel,T., Daiber,A. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity - Implications for mitochondrial oxidative stress and nitrate tolerance. Journal of Biological Chemistry 2007; 282(-1-):792-799. >>> Glyceryl trinitrate; Ethanol; Rat; 1007D; 4 days; Controls received mp w/ vehicle; cardiovascular; tolerance; animal info (male, Wistar, 250g.); nitroglycerin.
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; "Using the pellet in P7 rats produced a high rate of mortality from respiratory depression following pellet implantation and precluded parallel studies in the younger rats." (p. 254); Vetbond tissue adhesive was used.
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.).
P7942 Berni,R., Cacciani,F., Zaniboni,M., Savi,M., Bocchi,L., Lapucci,S., Razzetti,R., Pastore,F., Musso,E., Stilli,D. Effects of the alpha 2-adrenergic/DA2-dopaminergic agonist CHF-1024 in preventing ventricular arrhythmogenesis and myocyte electrical remodeling, in a rat model of pressure-overload cardiac hypertrophy. Journal of Cardiovascular Pharmacology 2006; 47(-2-):295-302. >>> CHF-1024; Saline; ascorbic acid; SC; Rat; 2ML4; 1 month; Controls received mp w/ vehicle; functionality of mp verified by plasma levels; dose-response (table 1); stability verified for at least 1 month (pg. 296); cardiovascular; post op. care (gentamicin); animal info (male, Wistar, 6 months old); "a clear dose dependency was found in CHF-1024 plasma levels, indicating a good performance of the osmotic pumps in drug release." (p. 299).
P9009 Castane,A., Soria,G., Ledent,C., Maldonado,R., Valverde,O. Attenuation of nicotine-induced rewarding effects in A2A knockout mice. Neuropharmacology 2006; 51(-3-):631-640. >>> Nicotine hydrogen tartrate; Saline; SC; Mice (knockout); 2001; 6, 7 days; Controls received mp w/ vehicle; dose-response (fig. 2); dependence; animal info (CD1, A2A KO, 30-35 g.).
P8188 Fahey,J.M., Pritchard,G.A., Reddi,J.M., Pratt,J.S., Grassi,J.M., Shader,R.I., Greenblatt,D.J. The effect of chronic lorazepam administration in aging mice. Brain Research 2006; 1118(--):13-24. >>> Lorazepam; PEG 400; SC; Mice; 1, 14 days; Controls received mp w/ vehicle; functionality of mp verified by lorazepam plasma concentrations; tolerance; animal info (male, CD-1, 2-3 months old, 10-12 months old, 22-24 months old).
P7591 Goktalay,G, Cavun,S., Levendusky,M.C., Hamilton,J.R., Millington,W.R. Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal. European Journal of Pharmacology 2006; 530(-1-2-):95-102. >>> Nicotine tartrate; SC; Rat; 2001; 4-7 days; Controls recived mp w/ saline; dependence; animal info (male, Sprague-Dawley, 250-300g).
P8971 Jang,S., Kim,H., Kim,D., Jeong,M.W., Ma,T., Kim,S., Ho,I.K., Oh,S. Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine. ARCHIVES OF PHARMACAL RESEARCH 2006; 29(-8-):677-684. >>> Morphine chloride; nalbuphine HCl; Saline; CSF/CNS; Rat; 2001; 3 days; Controls received mp w/ vehicle; comparison of IP injections vs. mp; tolerance; dependence; animal info (male, Sprague Dawley, 220-240 g.).
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.).
P7886 Jonkman,S., Markou,A. Blockade of nicotinic acetylcholine or dopamine D1-like receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminalis does not precipitate nicotine withdrawal in nicotine-dependent rats. Neuroscience Letters 2006; 400(-1-2-):140-145. >>> Nicotine hydrogen tortrate; Saline; SC; Rat; 2ML4; 4-8 weeks; Controls received mp w/ vehicle; pumps replaced after 28 days; dependence; animal info (male, Wistar).
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).
P7867 Malin,D.H., Lake,J.R., Smith,T.D., Khambati,H.N., Meyers-Paal,R.L., Montellano,A.L., Jennings,R.E., Erwin,D.S., Presley,S.E., Perales,B.A. Bupropion attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 2006; 184(-3-4-):494-503. >>> Nicotine bitartrate; bupropion HCL; Saline; SC; Rat; 2ML1; 7, 14 days; Controls received mp w/ vehicle; comparison of acute SC injection vs. mp; pumps replaced after 7 days; dependence; animal info (male, Sprague-Dawley, 389-468g.).
P7520 Mugnaini,M., Garzotti,M., Sartori,I., Pilla,M., Repeto,P., Heidbreder,C.A., Tessari,M. Selective down-regulation of 125IY0-alpha-conotoxin MII binding in rat mesostriatal dopamine pathway following continuous infusion of nicotine. Neuroscience 2006; 137(-2-):565-572. >>> Nicotine; SC; Rat; 2ML2; 14 days; Controls received mp w/ saline; comparison of acute SC injection vs. mp; dependence; animal info (male, Wistar 250-300 g).
P8025 O'Dell,L.E., Bruijnzeel,A.W., Smith,R.T., Parsons,L.H., Merves,M.L., Goldberger,B.A., Richardson,H.N., Koob,G.F., Markou,A. Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction. Psychopharmacology 2006; 186(-4-):612-619. >>> Nicotine; Saline; SC; Rat; 2ML2; 7-8 days; Controls received mp w/ vehicle; nicotine plasma levels taken; dependence; post op. care (Bacitracin ointment); animal info (male, Wistar).
P7795 Peleg-Raibstein,D., Sydekum,E., Russig,H., Feldon,J. Withdrawal from continuous amphetamine administration abolishes latent inhibition but leaves prepulse inhibition intact. Psychopharmacology 2006; 185(-2-):226-239. >>> Amphetamine; SC; Rat; 2001; 2ML1; 7 days; Controls received mp w/ vehicle or saline; dose-response (fig. 4); comparison of escalating SC dose injections vs. mp; dependence; post op. care (PVP-iodine); animal info (male, wistar, 300-350 g).
P7825 Pitas,G., Laurenzana,E.M., Williams,D.K., Owens,S.M., Gentry,W.B. Anti-phencyclidine monoclonal antibody binding capacity is not the only determinant of effectiveness, disproving the concept that antibody capacity is easily surmounted. Drug Metabolism and Disposition 2006; 34(-6-):906-912. >>> Phencyclidine HCL; Saline, sterile; SC; Rat; 2ML1; 4 days; Functionality of mp verified by serum PCP concentrations; half-life (pg. 907) 3.9 hours in rats; tolerance; animal info (male, Sprague-Dawley, 270-300g.).
P7863 Rezvani,A.H., Caldwell,D.P., Levin,E.D. Chronic nicotine interactions with clozapine and risperidone and attentional function in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY&BIOLOGICAL PSYCHIATRY 2006; 30(-2-):190-197. >>> Nicotine ditartrate; Saline; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; dependence; animal info (female, Sprague-Dawley, 60 days old, 289g.).
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.).
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.).
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.
P7835 Vann,R.E., Balster,R.L., Beardsley,P.M. Dose, duration, and pattern of nicotine administration as determinants of behavioral dependence in rats. Psychopharmacology 2006; 184(-3-4-):482-493. >>> Nicotine hydrogen tartrate; Saline, physiological; SC; Rat; 2ML2; 7, 12, 14, 15 days; Controls received mp w/ vehicle; dose-response (fig. 2); dependence; animal info (male, Sprague-Dawley); catheter tubing Lynch coil used to deliver 3 days nicotine, followed by 1 day saline, followed by remaining contents of mp (nicotine); compared with continuous nicotine administration.
P7790 Visser,S.A.G., Saellstroem,B., Forsberg,T., Peletier,L.A., Gabrielsson,J. Modeling drug- and system-related changes in body temperature: Application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats. Journal of Pharmacology and Experimental Therapeutics 2006; 317(-1-):209-219. >>> Clomethiazole edisilate; Saline; SC; Rat; 2001D; 24 hours; Controls received mp w/ vehicle; dose-response (fig. 4); comparison of SC injections vs. mp; tolerance; animal info (male, Sprague-Dawley, 301g.).
P8268 Wilmouth,C.E., Spear,L.P. Withdrawal from chronic nicotine in adolescent and adult rats. Pharmacology Biochemistry and Behavior 2006; 85(-3-):648-657. >>> Nicotine; Saline; SC; Rat; 2002; 7 days; Controls received sham surgery; functionality of mp verified by plasma cotinine levels; dependence; animal info (male, Sprague-Dawley, 28 days old, 60 days old).
P6875 Benavides,M., Laorden,M.L., Milanes,M.V. Involvement of 3',5';-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos expression and tyrosine hydroxylase levels during morphine withdrawal in the hypothalamic paraventricular nucleus and medulla oblongata catecholaminergic cell groups. Journal of Neurochemistry 2005; 92(-2-):246-254. >>> HA-1004; Water, sterile; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; no stress (see pg. 249); enzyme inhibitor (cAMP-dependent protein kinase A); dependence.
P6900 Berrendero,F., Mendizabal,V., Robledo,P., Galeote,L., Bilkei-Gorzo,A., Zimmer,A., Maldonado,R. Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. Journal of Neuroscience 2005; 25(-5-):1103-1112. >>> Nicotine; Saline; SC; Mice (knockout); 2001; 6 days; Dependence.
P7456 Bruijnzeel,A.W., Markou,A. Decreased sensitivity to the effects of dopamine D1-like, but not D2-like, receptor antagonism in the posterior hypothalamic region/anterior ventral tegmental area on brain reward function during chronic exposure to nicotine in rats. Brain Research 2005; 1058(-1-2-):91-100. >>> Nicotine hydrogen tartrate; Saline; SC; Rat; 2ML2; 2ML4; 6-28 days; Controls received mp w/ vehicle; dependence; animal info (male, Wistar, 300-350 g).
P7285 Dai,Y., Wang,H., Ogawa,A., Yamanaka,H., Obata,K., Tokunaga,A., Noguchi,K. Ca2+/calmodulin-dependent protein kinase II in the spinal cord contributes to neuropathic pain in a rat model of mononeuropathy. European Journal of Neuroscience 2005; 21(-9-):2467-2474. >>> KN93; KN92; MK-801; DMSO; saline; CSF/CNS (intrathecal); Rat; 1003D; 2001; 2002; 3,7,14 days; Controls received mp w/ vehicle, or KN92 control peptide; no stress (see pg. 2472); enzyme inhibitor (Ca/Calmodulin - dependent protein Kinase II); peptides; 10% DMSO; cannula tip location verified by dissection; NMDA receptor antagonist.
P7361 Daiber,A., Oelze,M., Sulyok,S., Coldewey,M., Schulz,E., Treiber,N., Hink,U., Muelsch,A., Scharffetter-Kochanek,K., Muenzel,T. Heterozygous deficiency of manganese superoxide dismutase in mice (Mn-SOD+/-): A novel approach to assess the role of oxidative stress for the development of nitrate tolerance. MOLECULAR PHARMACOLOGY 2005; 68(-3-):579-588. >>> Nitroglycerin; Ethanol; Mice; 1007D; 4 days; Controls received mp w/ vehicle; tolerance.
P7454 Daiber,A., Oelze,M., Coldewey,M., Kaiser,K., Huth,C., Schildknecht,S., Bachschmid,M., Nazirisadeh,Y., Ullrich,V., Muelsch,A., Muenzel,T., Tsilimingas,N. Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure. Biochemical and Biophysical Research Communications 2005; 338(-4-):1865-1874. >>> Nitroglycerin; Ethanol; SC; Rat; 1003D; 3 days; Controls received mp w/ vehicle; cardiovascular; tolerance; ischemia (cardiac); animal info (male, Wistar, 200 g).
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.
P7173 Davidson,C., Lee,T.H., Ellinwood,E.H. Acute and chronic continuous methamphetamine have different long-term behavioral and neurochemical consequences. NEUROCHEMISTRY INTERNATIONAL 2005; 46(-3-):189-203. >>> Methamphetamine; Saline, sterile; SC; Rat; 2ML1; 7 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; comparison of SC injections vs. mp; half-life (p. 189) 15-70 minutes in rodents; dependence; "MP treatment provides a better pharmakodynamic model for the human methamphetamine binger and may also better approximate the neuropathological outcome known in humans." (p. 200).
P8094 Duszczyk,M., Gadamski,R., Ziembowicz,A., Danysz,W., Lazarewicz,J.W. NMDA receptor antagonism does not inhibit induction of ischemic tolerance in gerbil brain in vivo. NEUROTOXICITY RESEARCH 2005; 7(-4-):283-292. >>> Memantine; SC; Gerbil; 1003D; 3 days; Comparison of acute IP injection vs. mp; tolerance; ischemia (cerebral); animal info (male, Mongolian, 12-13 wks old, 70g, carotid artery occlusion); mp primed 4 h. in 37 celsius saline; "steady state plasma levels at therapeutic range relevant to humans, were mimicked by using infusion pumps." (291).
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).
P7234 Grilli,M., Parodi,M., Raiteri,M., Marchi,M. Chronic nicotine differentially affects the function of nicotinic receptor subtypes regulating neurotransmitter release. Journal of Neurochemistry 2005; 93(-5-):1353-1360. >>> Nicotine hydrogen bitartrate; Saline; SC; Rat; 2ML2; 10 days; Controls received mp w/ vehicle; tolerance; dependence.
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.
P7270 Jonkman,S., Henry,B., Semenova,S., Markou,A. Mild anxiogenic effects of nicotine withdrawal in mice. European Journal of Pharmacology 2005; 516(-1-):40-45. >>> Nicotine tartrate; nicotine free base; Saline; SC; Mice; 2002; 14 days; Controls received mp w/ vehicle; dose-response (fig. 2); stress/adverse reaction: (see pg. 42) 5 of the mice receiving the highest dose of nicotine showed damage to the outer skin, most likely due to the high acidity of the nicotine; dependence; post op. care (Bacitracin zinc ointment).
P7256 Kenny,P.J., Markou,A. Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems. Journal of Neuroscience 2005; 25(-26-):6208-6212. >>> Nicotine hydrogen tartrate salt; Saline, sterile; SC; Rat; 2ML2; 2 weeks; Controls received mp w/ vehicle; dependence; post op. care (Bacitracin ointment).
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.
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).
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.
P7448 Li,M., Budin,R., Fleming,A.S., Kapur,S. Effects of chronic typical and atypical antipsychotic drug treatment on maternal behavior in rats. SCHIZOPHRENIA RESEARCH 2005; 75(-2-3-):325-336. >>> Haloperidol; olanzapine; Water, double distilled; acetic acid, glacial; SC; Rat; 2ML4; 3 weeks; Controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; comparison of daily SC injections vs. mp; tolerance; animal info (female, Sprague-Dawley, 60-100 day old, postpartum, 250-380 g).
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).
P7669 Lindblom,N., de Villiers,S.H.L., Semenova,S., Kalayanov,G., Gordon,S., Schilstroem,B., Johansson,A.M., Markou,A., Svensson,T.H. Active immunisation against nicotine blocks the reward facilitating effects of nicotine and partially prevents nicotine withdrawal in the rat as measured by dopamine output in the nucleus accumbens, brain reward thresholds and somatic signs. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2005; 372(-3-):182-194. >>> Nicotine hydrogen tartrate; SC; Rat; 2ML4; 28 days; Controls received mp w/ saline; half-life (pg. 192); dependence; post op. care (bacitracin); animal info (male, Wistar 250-300 g, 450-650 g).
P7711 Lindros,K.O., Jaervelaeinen,H.A. Chronic systemic endotoxin exposure: An animal model in experimental hepatic encephalopathy. METABOLIC BRAIN DISEASE 2005; 20(-4-):393-398. >>> Endotoxin, LPS; IV (jugular); Rat; 2ML4; 4 weeks; Functionality of mp verified by plasma endotoxin levels; tolerance; tubing contains pyrogen-free saline to delay agent delivery by 36 h..
P7280 Lodge,D.J., Grace,A.A. Acute and chronic corticotropin-releasing factor 1 receptor blockade inhibits cocaine-induced dopamine release: Correlation with dopamine neuron activity. Journal of Pharmacology and Experimental Therapeutics 2005; 314(-1-):201-206. >>> CRA-0450; Water, deionized; Tween 80; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle; comparison of acute icv injections vs. mp; ALZET brain infusion kit 1 used; tolerance; post op. care (pramoxine HcL/Neomycin, Tylenol); CRF1 receptor antagonist; 2% Tween 80.
P7560 Lu,X.C.M., Williams,A.J., Wagstaff,J.D., Tortella,F.C., Hartings,J.A. Effects of delayed intrathecal infusion of an NMDA receptor antagonist on ischemic injury and peri-infarct depolarizations. Brain Research 2005; 1056(-2-):200-208. >>> CGX-1007; Saline; CSF/CNS (intrathecal, cisterna magna); Rat; 2001D; 16 hours; Controls received mp w/ vehicle; dose-response (fig. 1); no stress (see pg. 203); dose-dependent paralysis and mortality; peptides; ischemia (cerebral); animal info (male, Sprague-Dawley, 275-350 g); agent also known as Conantokin-G; NMDA receptor antagonist; middle cerebral artery occlusion; stretched PE-10 tubing to a PE-60 connection piece.
P7716 Prokai,L., Zharikova,A.D., Stevens,SM Jr 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).
P6970 Shoaib,M., Bizarro,L. Deficits in a sustained attention task following nicotine withdrawal in rats. Psychopharmacology 2005; 178(-2-3-):211-222. >>> Nicotine bitartrate; Saline, isotonic; NaOH; SC; Rat; 7 days; Controls received mp w/ vehicle; nicotine plasma levels taken; dose-response (p. 9); dependence; behavioral study.
P7735 Silva-Barrat,C., Velluti,J., Szente,M., Batini,C., Champagnat,J. Exaggeration of epileptic-like patterns by nicotine receptor activation during the GABA withdrawal syndrome. Brain Research 2005; 1042(-2-):133-143. >>> Aminobutyric acid, gamma; CSF/CNS (somatomotor cortex); Rat; 2001; 5 days; Controls received mp w/ saline or no treatment; dependence; animal info (male, wistar).
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.
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).
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“In order to investigate the in vivo role of MMPs, we established a rodent model of glioma progression... We chose continuous infusion using an osmotic pump as the method for delivering TIMP into the tumor. This paradigm allowed aggressive glioma development and circumvented the problem of the blood brain barrier disturbing reagent delivery following intravenous delivery.” Takahashi et al., Pharmacological Research 2002;46(2):155-163.