References on the Administration of Drugs of Abuse (including Amphetamines, Barbiturates, Cocaine, GHB, Heroin, Nicotine, and PCP) Using ALZET® Osmotic Pumps

1. Amphetamine

16028 Iijima, M., Koike, H., Chaki, S. Effect of an mGlu2/3 receptor antagonist on depressive behavior induced by withdrawal from chronic treatment with methamphetamine. Behav Brain Res 2013; 246(--):24-8. >>> methamphetamine; SC; rat; 2ML1; animal info: male, Sprague-Dawley, 5-weeks old; dependence; behavioral testing (forced swimming test; ); mp were used to infuse methamphetamine to induce withdrawl symptoms in mice; dose: 2.5, or 5 mg/kg/day.

15967 Iijima, M., Koike, H., Chaki, S. Effect of an mGlu2/3 receptor antagonist on depressive behavior induced by withdrawal from chronic treatment with methamphetamine. Behav Brain Res 2013; 246(--):24-8. >>> methamphetamine (MAP); saline; SC; rat; 2ML1; animal info: male, Sprague-Dawley, 5 wks old; tolerance studies; post op care: pumps removed under sodium pentobarbital anesthesia; behavioral testing: forced swimming test, locomotor activity; mp used to infuse methamphetamine to induce a withdrawal-like effect in rats to study the effect of LY341495 (mGlu2/3 receptor antagonist) on withdrawal-induced depressive behavior; dose 2, 5 mg/kg/day.

15052 Nanaware-Kharade, N., Thakkar, S., Gonzalez, GA III, Peterson, E.C., Peterson, E.C. A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments. SCIENTIFIC REPORTS 2015; 5(--):U1-U10. >>> Methamphetamine; SC; Rat; Animal info (male, Sprague Dawley, adult, 280-310g); functionality of mp verified by blood levels; dependence; cardiovascular;.

14959 Harris, A.C., LeSage, M.G., Shelley, D., Perry, J.L., Pentel, P.R., Owens, S.M., Harris, A.C. The Anti-(+)-Methamphetamine Monoclonal Antibody mAb7F9 Attenuates Acute (+)-Methamphetamine Effects on Intracranial Self-Stimulation in Rats. PLoS One 2015; 10(--):U408-U420. >>> Methamphetamine hydrochloride; Saline; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 275-300g); functionality of mp verified by elevations in ICSS; behavioral testing (ICSS); dependence; pumps removed after 7 days;.

14903 Czoty, P.W., Tran, P., Thomas, L.N., Martin, T.J., Grigg, A., Blough, B.E., Beveridge, T.J.R., Czoty, P.W. Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats. PSYCHOPHARMACOLOGY 2015; 232(--):2405-2414. >>> Amphetamine, D-; phenmetrazine; Saline; SC; Rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague-Dawley, 300-350g); pumps replaced every 7 days; behavioral testing (cocaine self-administration, food self-administration); dependence;.

14670 Blum, I.D., Zhu, L., Moquin, L., Kokoeva, M.V., Gratton, A., Giros, B., Storch, K.F., Storch, K.F. A highly-tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal. ELIFE 2014; 3(--):U146-U189. >>> Methamphetamine; Saline; SC; Mice; 1002; Animal info (Bmal1 -/-, ); behavioral testing (locomotor activity running wheels); dependence; delayed delivery; catheter filled with saline for 4 day recovery; used plastics one catheter;.

13932 Zimmer, B.A., Chiodo, K.A., Roberts, D.C.S. Reduction of the reinforcing effectiveness of cocaine by continuous D-amphetamine treatment in rats: importance of active self-administration during treatment period. Psychopharmacology 2014; 231(-5-):949-954. >>> Amphetamine, D-; Saline, sterile; SC; Rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 12 week old, 350g); behavioral testing (cocaine self-administration); dependence; pumps removed on day 7; used amphetamine concentration of approx 73ug/ul..

13716 Bauer, C.T., Banks, M.L., Negus, S.S., Negus, S.S. The effect of chronic amphetamine treatment on cocaine-induced facilitation of intracranial self-stimulation in rats. Psychopharmacology 2014; 231(--):2461-2470. >>> Amphetamine; Saline; SC; Rat; 2ML4; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 311-406g); post op. care (Ketoprofen 5 mg/kg); behavioral testing (cocaine self administration); dependence; pumps removed after 14 days;.

13619 Rau, T.F., Kothiwal, A.S., Rova, A.R., Brooks, D.M., Rhoderick, J.F., Poulsen, A.J., Hutchinson, J., Poulsen, D.J. Administration of low dose methamphetamine 12 h after a severe traumatic brain injury prevents neurological dysfunction and cognitive impairment in rats. Experimental Neurology 2014; 253(-;-):31-40. >>> Methamphetamine; IV (femoral); Rat; 2001D; Controls received mp w/ vehicle; animal info (male, Wistar, 350-500g); functionality of mp verified by plasma serum levels; dose-response (pg.33); behavioral testing (foot fault assessment, morris water maze); pumps implanted in inguinal crease; catheter preloaded with 50% dextrose/50% heparin; pumps removed after 61-65hours;.

13195 Ding, G.L., Chopp, M., Poulsen, D.J., Li, L., Qu, C.S., Li, Q.J., Nejad-Davarani, S.P., Budaj, J.S., Wu, H.T., Mahmood, A., Jiang, Q. MRI of Neuronal Recovery after Low-Dose Methamphetamine Treatment of Traumatic Brain Injury in Rats. PLoS One 2013; 8(-4-):U175-U183. >>> Methamphetamine; IV; Rat; Controls received mp w/ saline; animal info. (male, wistar rats, 200-300 g); functionality of mp verified by MRI measurement of fractional anisotropy.

12969 Rau, T.F., Kothiwal, A.S., Rova, A.R., Brooks, D.M., Poulsen, D.J. Treatment with low-dose methamphetamine improves behavioral and cognitive function after severe traumatic brain injury. JOURNAL OF TRAUMA AND ACUTE CARE SURGERY 2012; 73(-;-):S165-S172. >>> Methamphetamine; IV (femoral); Rat; 2001D; Control animals received mp w/ saline; animal info (Wistar, male, adult, 400 g); PE50 tubing used.

11978 Bhatia, K.S., Szabo, S.T., Fowler, J.C., Wetsel, W.C., Lee, T.H. Reversal of long-term methamphetamine sensitization by combination of pergolide with ondansetron or ketanserin, but not mirtazapine. Behavioural Brain Research 2011; 223(-1-):227-232. >>> Methamphetamine hydrochloride; Saline; SC; Rat; 2ML1; Controls received mp w/ vehicle; animal info (Sprague Dawley, male, 275-300 g); functionality of mp verified via residual volume.

11508 Miyata, H., Itasaka, M., Kimura, N., Nakayama, K. Decreases in Brain Reward Function Reflect Nicotine- and Methamphetamine-Withdrawal Aversion in Rats. Current Neuropharmacology 2011; 9(-1-):63-67. >>> Nicotine; methamphetamine; Saline; SC; Rat; 2001; Controls received mp w/ vehicle; animal info (Sprague Dawley, male, 332-396 g).

10745 Kitanaka, N., Kitanaka, J., Tatsuta, T., Tanaka, K., Watabe, K., Nishiyama, N., Morita, Y., Takemura, M. Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice. Neurochemical Research 2010; 35(-5-):749-760. >>> Methamphetamine; Saline, sterile; SC; Mice; 2002; Controls received mp w/ vehicle; animal info (ICR, 38-55 g); wound clips used; behavioral testing (tail suspension).

10680 Chiodo, K.A., Roberts, D.C.S. Decreased reinforcing effects of cocaine following 2 weeks of continuous d-amphetamine treatment in rats. Psychopharmacology 2009; 206(-3-):447-456. >>> Amphetamine, D-; Saline, sterile; SC; Rat; 2001; Animal info (male, Sprague-Dawley, 350 g).

10662 Der-Avakian, A., Markou, A. NEONATAL MATERNAL SEPARATION EXACERBATES THE REWARD-ENHANCING EFFECT OF ACUTE AMPHETAMINE ADMINISTRATION AND THE ANHEDONIC EFFECT OF REPEATED SOCIAL DEFEAT IN ADULT RATS. Neuroscience 2010; 170(-4-):1189-1198. >>> Amphetamine; SC; Rat; 2ML1; Controls received mp w/saline; animal info (maternally separated, Long Evans); behavioral testing (maternal behavior).

10612 White, S.J., Laurenzana, E.M., Gentry, W.B., Hendrickson, H.P., Williams, D.K., Ward, K.W., Owens, S.M. Vulnerability to (+)-Methamphetamine Effects and the Relationship to Drug Disposition in Pregnant Rats during Chronic Infusion. TOXICOLOGICAL SCIENCES 2009; 111(-1-):27-36. >>> Methamphetamine; amphetamine; SC; Rat (pregnant); 2ML2; Controls received mp w/ saline; animal info (female, Sprague-Dawley, 180-270 g); dose-response (fig. 1); no stress (see pg.) There were no observable adverse health changes"pg 30; stress/adverse reaction (see pg. 30)"Two rats (in the 10- and 13.2-mg/kg/day groups) developed an abscess at the pump site, which appeared to be confined to the sc minipump implantation site."pg 30;"one animal chewed her skin at the pump site, exposing the osmotic pump"pg 30."ClS corrected for the bioavailability or fraction of the drug absorbed (ClS/F) was calculated using the equation, ClS/F = infusion rate/CSS, where CSS is the steady-state drug concentration"pg 29.

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2. Cocaine

15697 Radke, A.K., Zlebnik, N.E., Carroll, M.E., Radke, A.K. Cocaine withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 2015; 129(--):51-55. >>> Cocaine hydrochloride; Saline, sterile; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (male, Holtzmann/Harlan Sprague Dawley); no stress (see pg.53); post op. care (topical antibiotic ointment); behavioral testing (saccharin intake); dependence; pumps removed after 2 weeks;.

13906 Pudiak, C.M., KuoLee, R., Bozarth, M.A., Pudiak, C.M. Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions. Pharmacology Biochemistry and Behavior 2014; 122(--):246-252. >>> Cocaine; Saline; sodium metabisulfate; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (male, Long-Evans, 275-350g); functionality of mp verified by residual volume; 0.3% sodium metabisulfate used to prevent degredation; stress/adverse reaction: (see pg.294); post op. care (neosporin); dependence;"Cocaine delivered continuously via osmotic minipump may better mimic the high drug-plasma concentrations maintained by an addict during a binge than daily administered cocaine injections."pg 250; pumps removed after 14 days; pumps primed at 37C for at least 4 hours;.

13879 Narayana, P.A., Herrera, J.J., Bockhorst, K.H., Esparza-Coss, E., Xia, Y., Steinberg, J.L., Moeller, F.G. Chronic cocaine administration causes extensive white matter damage in brain: Diffusion tensor imaging and immunohistochemistry studies. PSYCHIATRY RESEARCH-NEUROIMAGING 2014; 221(-3-):220-230. >>> Cocaine; Saline; SC; Rat; 2ML4; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 280-300g); behavioral testing (fine motor movement; ambulation; rearing activities; general motor behavior); dependence; MRI; pumps primed for 24 hours in 37C saline;.

13728 Caputi, F.F., Di Benedetto, M., Carretta, D., Candia, S.B.D., D'Addario, C., Cavina, C., Candeletti, S., Romualdi, P. Dynorphin/KOP and nociceptin/NOP gene expression and epigenetic changes by cocaine in rat striatum and nucleus accumbens. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY&BIOLOGICAL PSYCHIATRY 2014; 49(-;-):36-46. >>> Cocaine; SC; Rat; 2001; Controls received mp w/ saline; animal info (male, Sprague Dawley, 200-250g); dependence; pumps primed overnight in 37C saline;.

12447 Stoker, A.K., Olivier, B., Markou, A. Involvement of metabotropic glutamate receptor 5 in brain reward deficits associated with cocaine and nicotine withdrawal and somatic signs of nicotine withdrawal. Psychopharmacology 2012; 221(-2-):317-327. >>> Nicotine; cocaine hydrochloride; Saline, sterile; SC; IP; Mice; 2004; 1003D; Controls received mp w/ vehicle; animal info (mGlu5 KO, wt).

11975 Stoker, A.K., Markou, A. Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice. Behavioural Brain Research 2011; 223(-1-):176-181. >>> Cocaine hydrochloride; Saline, sterile; IP; Mice; 1003D; Controls received mp w/ saline; animal info (C57BL/6, male, 7-8 wks old) withdrawal;"continuous cocaine administration via intraperitoneal osmotic minipumps is an excellent tool for the assessment of the effects of cocaine administration and withdrawal on various behavioral measures."pg 180.

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3. GHB

6910 Szabo, S.T., Gold, M.S., Goldberger, B.A., Blier, P. Effects of sustained gamma-hydroxybutyrate treatments on spontaneous and evoked firing activity of locus coeruleus norepinephrine neurons. Biological Psychiatry 2004; 55(-9-):934-939. >>> Hydroxybutyrate, gamma-; Saline; SC; Rat; Controls received mp w/ vehicle; dependence; agent is a drug of abuse, known as"liquid ecstacy"or GHB (sodium oxybate); pump model not listed.

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4. Heroin

15755 Stephen Daniels, &Paul Marshall, &Francesco Leri. Alterations of naltrexone-induced conditioned place avoidance by pre-exposure to high fructose corn syrup or heroin in Sprague–Dawley rats. Psychopharmacology 2016; (-233-):425-433. >>> Heroin; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (male, Spargue Dalwley, 175-200g); behavioral testing (place conditioning); used wound clips; Dose (3.5 mg/kg/day);.

12743 Williams, A.M., Reis, D.J., Powell, A.S., Neira, L.J., Nealey, K.A., Ziegler, C.E., Kloss, N.D., Bilimoria, J.L., Smith, C.E., Walker, B.M. The effect of intermittent alcohol vapor or pulsatile heroin on somatic and negative affective indices during spontaneous withdrawal in Wistar rats. Psychopharmacology 2012; 223(-1-):75-88. >>> Heroin; Saline; SC; Rat; 2ML4; Control animals received mp w/ vehicle; animal info (Wistar, male, 70 days old); pulsatile delivery;"By filling the pumps with saline and attaching polyethylene (PE60) tubing to the pump, based on the tubing inner diameter and pump flow rate characteristics, the volume needed for different infusion periods (e.g., 14- or 10-h periods) could be determined"; pulsatile delivery; good methods, pg 78; image of pump with connected Lynch coil; wound clips used; post op. care (Baytril); behavioral testing (elevated plus mazel forced swim test).

10836 Kest, B., Smith, S.B., Schorscher-Petcu, A., Austin, J.S., Ritchie, J., Klein, G., Rossi, G.C., Fortin, A., Mogil, J.S. Gnao1 (G-alphao PROTEIN) IS A LIKELY GENETIC CONTRIBUTOR TO VARIATION IN PHYSICAL DEPENDENCE ON OPIOIDS IN MICE. Neuroscience 2009; 162(-4-):1255-1264. >>> Morphine; heroin; Saline; SC; Mice; 2001; Animal info (Naive, adult, 7-12 wks old, male, AcB/BcA).

9944 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).

6462 Azar, M.R., Ahmed, S.H., Lintz, R., Gutierrez, T., Stinus, L., Koob, G.F. A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal. Journal of Neuroscience Methods 2004; 135(-1-2-):129-135. >>> Heroin; Saline; SC; Rat; 2ML2; Comparison of sc injections&pellet vs. mp; dependence; 3 day recovery period; pumps connected to a novel gating device to allow on-off delivery; assembly schematic (p. 131); infusions were delivered in 48 hour intervals; animal info (m, wistar, 300-380 grams).

3240 Shaham, Y., Rajabi, H., Stewart, J. Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal. J. Neurosci 1996; 16(-5-):1957-1963. >>> Heroin; SC; rat; 2002; controls received mp with saline or sham operation; dependence.

588 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; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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5. Nicotine

16319 Yang, J., Liu, A. Y., Tang, B., Luo, D., Lai, Y. J., Zhu, B. L., Wang, X. F., Yan, Z., Chen, G. J. Chronic nicotine differentially affects murine transcriptome profiling in isolated cortical interneurons and pyramidal neurons. BMC Genomics 2017; 18(-1-):194. >>> Nicotine hydrogen tartrate; Saline; SC; Mice; 2002; Controls received mp w/ vehicle; animal info (male mice 20 g, 5–7 weeks old); Dose (48 mg/kg/d);.

16280 Younes-Rapozo, V., Moura, E. G., Manhaes, A. C., Pinheiro, C. R., Carvalho, J. C., Barradas, P. C., de Oliveira, E., Lisboa, P. C. Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats. J Neuroendocrinol 2015; 27(-12-):887-98. >>> Nicotine; Saline; SC; Rat (pregnant); 2ML2; Controls received mp w/ vehicle; animal info (Wistar rats, pregnant); functionality of mp verified by plasma levels; Pumps primed for 24 hrs; Resultant plasma level (cotinine 25 ng/ml); Dose (6 mg/kg/d);.

16271 Vivekanandarajah, A., Waters, K. A., Machaalani, R. Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem. Int J Dev Neurosci 2015; 47(-Pt B-):183-91. >>> Nicotine Hydrogen Tartrate; water; IP; Pig (mini); 2ML2; Controls received mp w/ vehicle; animal info (piglets); functionality of mp verified by blood and urine samples; toxicology; Dose (2 mg/kg/d); Resultant plasma level (20.3±2.5 ng/mL);.

16249 Slotkin, T. A., Skavicus, S., Seidler, F. J. Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos. Toxicology 2015; 338(--):8-16. >>> Nicotine Bitartrate; Water, bacteriostatic; SC; Rat (pregnant); 2ML2; Controls received mp w/ vehicle; animal info (pregnant Sprague-Dawley rats, 211-217g); animal info (pregnant Sprague-Dawley rats, 211-217g); dependence; Wound clips used; Dose (3 mg/kg/day);.

16246 Shih, P. Y., McIntosh, J. M., Drenan, R. M. Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident Nicotinic Receptors in Medial Habenula. Mol Pharmacol 2015; 88(-6-):1035-44. >>> Nicotine hydrogen-tartrate salt; Saline; SC; mice; 2004; Controls received mp w/ vehicle; animal info (Adult (2–3 months old) mice; C57BL/6 wild-type); functionality of mp verified by plasma levels; functionality of mp verified by plasma levels; dependence; Dose (1 mg/kg/hr); Resultant plasma level (0.3 uM; 40 ng/ml);.

16234 Renaud, S. M., Pickens, L. R., Fountain, S. B. Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats. Neurotoxicol Teratol 2015; 48(--):40-8. >>> Nicotine bitartrate; Water, bacteriostatic; SC; rat; 2004; Controls received mp w/ vehicle; animal info: female Long Evans rats; functionality of mp verified by behavioral test; dose-response (pg 43-44); neurodegenerative (learning impairments); behavioral testing (serial multiple choice); effects of adolescent nicotine exposure on learning in adulthood; anesthetized under isoflurane; Dose: 0.033 mg/h.

16215 Muelken, P., Schmidt, C. E., Shelley, D., Tally, L., Harris, A. C. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation. PLoS One 2015; 10(-12-):e0144553. >>> Nicotine bitartrate; Saline, physiological; SC; rat; 2ML2; Controls received mp w/ vehicle; animal info (Male Wistar rats, 275–300 g); functionality of mp verified by elevations in intracranial self-stimulation; dose-response (pg 8, 9); post op. care (buprenorphine, ceftriaxone); behavioral testing (intracranial self-stimulation pg 4); Dependence, nicotine; “elevations in ICSS thresholds beginning on the second day ofinfusion” (Pg. 1); primed in saline for 1 hour prior to implantation; Dose (3.2 mg/kg/day);.

16195 Lee, B. G., Anastasia, A., Hempstead, B. L., Lee, F. S., Blendy, J. A. Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice. Nicotine Tob Res 2015; 17(-12-):1428-35. >>> Nicotine hydrogen tartrate salt; Saline; SC; mice; 2002; Controls received mp w/ vehicle; animal info: Mice (23–38 g; 2–4 months old); functionality of mp verified by behavior; behavioral testing (withdrawal measurements); Dependence nicotine; Dose: 18 mg /kg/day.

16180 Simmons, S. J., Gentile, T. A., Mo, L., Tran, F. H., Ma, S., Muschamp, J. W. Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats. Behav Brain Res 2016; 314(--):226-33. >>> Nicotine; Saline; SC; Rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, adult); behavioral testing (open field); dependence; used staples (9mm); Dose (3.16 mg/kg/day free base);.

16137 Hoegberg, B. G., Lomazzo, E., Lee, N. H., Perry, D. C. Regulation of alpha4beta2alpha5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine. Neuropharmacology 2015; 99(--):347-55. >>> Nicotine hydrogen tartrate; Saline; SC; SC; 2002; Controls received mp w/ vehicle; animal info: Sprague Dawley rats; dose-response (pg 350); post op. care (buprenorphine); dependence; Dose: 17 mg/kg/day.

16112 de la Pena, J. B., Ahsan, H. M., Tampus, R., Botanas, C. J., dela Pena, I. J., Kim, H. J., Sohn, A., dela Pena, I., Shin, C. Y., Ryu, J. H., Cheong, J. H. Cigarette smoke exposure during adolescence enhances sensitivity to the rewarding effects of nicotine in adulthood, even after a long period of abstinence. Neuropharmacology 2015; 99(--):9-14. >>> Nicotine; SC; rat; 2ML2; Controls received sham pumps; animal info: Male Sprague Dawley; dose-response (pg 12); behavioral testing (conditioned place preferences (CPP) and self-administration tests); dependence, nicotine; Dose: 3.2 mg/kg/day.

16104 Cerpa, V. J., Aylwin Mde, L., Beltran-Castillo, S., Bravo, E. U., Llona, I. R., Richerson, G. B., Eugenin, J. L. The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome. Am J Respir Cell Mol Biol 2015; 53(-4-):489-99. >>> Nicotine bitartrate; saline; SC; Mice (pregnant); 2004; Controls received mp w/ vehicle; animal info 5-7 days pregnant adult mice; dependence, nicotine; Pump delivery mimics the tendency of smokers to maintain a constant blood level of nicotine throughout the day; Dose: (60 mg kg-1 day-1).

16084 Zhao, L., Zhuang, J., Xu, F. Bronchopulmonary C-fibers'IL1RI contributes to the prolonged apneic response to intra-atrial injection of capsaicin by prenatal nicotinic exposure in rat pups. Toxicol Appl Pharmacol 2016; 303(--):58-64. >>> Nicotine; methyllycaconitine; Saline; SC; Rat; 2004; Controls received mp w/ vehicle; animal info (female, Sprague Dawley, 250-350g); pumps replaced every 28 days; Multiple pumps per animal (2); long-term study; teratology; MLA is an a7nAChR antagonist; methyllycaconitine aka MLA; Dose (nicotine 6 mg/kg/day; MLA 3 mg/kg/day);.

16027 Hussmann, G. P., DeDominicis, K. E., Turner, J. R., Yasuda, R. P., Klehm, J., Forcelli, P. A., Xiao, Y., Richardson, J. R., Sahibzada, N., Wolfe, B. B., Lindstrom, J., Blendy, J. A., Kellar, K. J. Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J Neurochem 2014; 129(-4-):721-31. >>> nicotine; sazetidine-A; varenicline; saline; SC; rat, mice; Controls received mp w/ saline vehicle; animal info (male adult Sprague-dawley rats, 8 weeks, 240 g; male 129SvJ;C57BL/6J F1 hybrid mice, 6 weeks, 25-30 g ); functionality of mp verified by protein binding in rat cortex ; pumps replaced after 2 weeks; 1 additional week of infusion for mice, 4 additional weeks of infusion for rats; post op. care (buprenorphine or ketoprofen injected for analgesia); behavioral testing (memory retention and attention in rats); Saz-A aka sazetidine-A; Rats Dose: 6 mg/kg/day nicotine, 4.7 mg/kg/day saz-A, 1.2 mg/kg/day vareniclineMice Dose: 18 mg/kg/day nicotine, 1.8 mg/kg/day saz-A, 1.8 mg/kg/day varenicline.

16026 Huang, L. T., Chou, H. C., Lin, C. M., Yeh, T. F., Chen, C. M. Maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis in rats. Neonatology 2014; 106(-2-):94-101. >>> nicotine tartrate; saline; SC; rats; 2ML2, 2ML4; Controls received mp w/ sterile saline vehicle; animal info (Sprague-dawley rats ages 7-21 days); functionality of mp verified by plasma levels; Western Blot analysis, histological exams ; Dose: 40 ug/ul nicotine tartrateà6mg/kg/day; Resultant plasma level (resembling moderate to heavy human smokers);.

16017 Gorini, C., Jameson, H., Woerman, A. L., Perry, D. C., Mendelowitz, D. Prenatal nicotine exposure enhances the trigeminocardiac reflex via serotonin receptor facilitation in brainstem pathways. J Appl Physiol (1985) 2013; 115(-4-):415-21. >>> nicotine; SC; rat; animal info: female, Sprague-Dawley, day 3 of gestation, pregnant; relationship between prenatal nicotine exposure and SIDS (sudden infant death syndrome); cardiovascular; dose: 6 mg/kg/day.

15983 Jackson, K. J., Jackson, A., Carroll, F. I., Damaj, M. I. Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302 on nicotine withdrawal in mice. Neuropharmacology 2015; 97(--):270-4. >>> Nicotine hydrogen tartrate salt; Saline; SC; Mice; 2002; Controls received mp w/ vehicle; animal info (male, ICR, 8-10 weeks old); behavioral testing (elevated plus maze; hyperalgesia); dependence; Dose (24 mg/kg/day);.

15928 Pinheiro, C. R., Oliveira, E., Manhaes, A. C., Fraga, M. C., Claudio-Neto, S., Younes-Rapozo, V., Lotufo, B. M., Moura, E. G., Lisboa, P. C. Exposure to nicotine increases dopamine receptor content in the mesocorticolimbic pathway of rat dams and offspring during lactation. Pharmacol Biochem Behav 2015; 136(--):87-101. >>> Nicotine; Saline; SC; Rat (lactating); 2ML2; Controls received mp w/ vehicle; animal info (female, Wistar, PN2); Dose (6 mg/kg/day); Resultant plasma level (cotinine dams serum 239 ng/ml and in milk 226 ng/ml; cotinine levels in 15 days old pumps 20 ng/ml);.

15878 Slotkin, T. A., Skavicus, S., Card, J., Stadler, A., Levin, E. D., Seidler, F. J. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci 2015; 147(-1-):178-89. >>> Nicotine; tobacco smoke extract; DMSO; Rat; 2ML4; Controls received mp w/ vehicle; animal info (female, non-pregnant, adult, Sprague Dawley); functionality of mp verified by plasma nicotine levels; dose-response (pg 181); teratology; Dose (Nicotine free base 0.2 or 2 mg/kg/day; TSE 0.18 mg/kg/day);.

15861 Zhao, L., Zhuang, J., Zang, N., Lin, Y., Lee, L. Y., Xu, F. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response. Toxicol Appl Pharmacol 2016; 290(--):107-15. >>> Nicotine; mecamylamine; methyllycaconitine; SC; Rat (pregnant); 2004; Controls received mp w/ vehicle; animal info (female, Sprague Dawley, 250-300g); pumps replaced on GD7; Multiple pumps per animal (2); no stress (see pg. 110-111); teratology; Dose (Nicotine 6 mg/kg/day; mecamylamine 0.03 mg/kg/day; methyllycaconitine 3 mg/kg/day);.

15811 C.R. Pinheiro, E.G.Moura, A.C.Manhães, M.C. Fraga, S. Claudio-Neto, V. Younes-Rapozo, A.P. Santos-Silva, B.M. Lotufo, E. Oliveira, P.C. Lisboa. Maternal nicotine exposure during lactation alters food preference,anxiety-like behavior and the brain dopaminergic reward system in theadult rat offspring. Physiol Behav 2015; 149(--):131-141. >>> Nicotine; Saline; SC; Rat (lactating); 2ML2; animal info (female, Wistar, PN2); behavioral testing (food preference);“Exposure to nicotine through subcutaneous osmotic minipump infusion was used to avoid the adverse effects of nicotine peaks” pg 132; Dose (6 mg/kg/day); Resultant plasma level (25 ng/ml,"similar to those found in typical smokers");.

15807 Vinay Parikh, Robert D. Cole,, Purav J. Patel,, Rachel L. Poole,, Thomas J. Gould. Cognitive control deficits during mecamylamine-precipitatedwithdrawal in mice: Possible links to frontostriatal BDNF imbalance. NEUROBIOLOGY OF LEARNING AND MEMORY 2016; 128(--):110-116. >>> Nicotine hydrogen tartrate; Saline, sterile; SC; Mice; 1004; Controls received mp w/ vehicle; animal info (male, C57BL6J, 8-10 weeks old, 20-25g); functionality of mp verified by plasma cotinine levels; behavioral testing (visual discriminations, operant training); dependence; Dose (18 mg/kg/day free base resultedin 100-150 ng/ml plasma cotinine levels);.

15806 C C Paccola and S M Miraglia. Prenatal and lactation nicotine exposure affects Sertoli cell and gonadotropin levels in rats. REPRODUCTION 2016; 151(--):117-133. >>> Nicotine hydrogen tartrate salt; Water, bacteriostatic; SC; Rat (pregnant; lactating); 2ML4; Controls received mp w/ vehicle; animal info (GD1); pumps replaced after birth; no stress (see pg. 123); cyanoacrylate adhesive;“There were no cases of stillbirth, birth defects, or other signs of toxicity that could be attributed to nicotine. Behavioral changes in the rat dams that could be attributed to the stress caused by the osmotic minipump implant were also not evidenced. Body weights were obtained at every chosen age of killing and no differences were found when nicotine and control groups were compared, at any ageequivalent subgroup. The” pg 123; Dose (2 mg/kg/day);.

15789 Chun Li, Hong Sun, Denise M. Arrick, William G. Mayhan. Chronic nicotine exposure exacerbates transient focal cerebral ischemiainduced brain injury. J Appl. Physiol 2016; 120(--):328-333. >>> Nicotine; Saline; SC; Rat; Controls received mp w/ saline; animal info (male, Sprague Dawley, 250-300g); ischemia (cerebral);“The subcutaneous osmotic minipump releases nicotine at a constant rate, which resulted in stable plasma nicotine and cotinine levels that match the chronic smokers. The doses of nicotine used in the present study have been reported to result in stable plasma nicotine levels corresponding reasonably well with plasma levels in habitual light (0.5–1 pack/day) and moderate (2 packs/day) smokers” pg 331; traumatic brain injury; Dose (2 or 4 mg/kg/day);.

15768 Erivan Clementino Gualberto Jr., Letícia Helena Theodoro, Mariellén Longo, Vivian Cristina Noronha Novaes, Maria JoséHitomi Nagata, Edilson Ervolino, Valdir Gouveia Garcia. Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis. Lasers med sci 2016; 31(--):83-94. >>> Nicotine; Saline; SC; Rat; 2006; Controls received mp w/ vehicle; animal info (female, Wistar, 3 months old, 266+/-6.5g); pumps replaced after 40 days; Dose (6 mg/kg/day);.

15747 Kang Chen,, Sakura Nakauchi,, Hailing Su,, Saki Tanimoto,, Katumi Sumikawa. Early postnatal nicotine exposure disrupts the a2* nicotinic acetylcholine receptor-mediated control of oriens-lacunosum moleculare cells during adolescence in rats. Neuropharmacology 2016; 101(--):57-67. >>> Nicotine; Saline; SC; Rat (lactating); 2ML2; animal info (female, Sprague Dawley, ); teratology; Dose (6 mg/kg/day);.

15227 Natividad, L.A., Torres, O.V., Friedman, T.C., O'Dell, L.E. Adolescence is a period of development characterized by short- and long-term vulnerability to the rewarding effects of nicotine and reduced sensitivity to the anorectic effects of this drug. BEHAVIOURAL BRAIN RESEARCH 2013; 257(-;-):275-285. >>> Nicotine; SC; Rat; 2ML2; Controls received sham surgery; animal info (male, Wistar); dependence; pumps removed after 14 days;.

15208 Cunningham, C.S., Moerke, M.J., McMahon, L.R., McMahon, L.R. The discriminative stimulus effects of mecamylamine in nicotine-treated and untreated rhesus monkeys1734. BEHAVIOURAL PHARMACOLOGY 2014; 25(--):296-305. >>> Nicotine; Saline; SC; Monkey (Rhesus); 2ML4; Controls received mp w/ vehicle; animal info (Macaca mulatta, rhesus monkey, adult); pumps replaced every 28 days; behavioral testing (stimulus-shock termination);.

15198 Caine, S.B., Collins, G.T., Thomsen, M., Wright, C., Lanier, R.K., Mello, N.K. Nicotine-Like Behavioral Effects of the Minor Tobacco Alkaloids Nornicotine, Anabasine, and Anatabine in Male Rodents. EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY 2014; 22(-1-):9-22. >>> Nicotine; SC; Mice; 1004; Animal info (male, Swiss Webster, 4-8 weeks old); dependence; pumps removed after 28 days;.

15167 Zanos, P., Georgiou, P., Metaxas, A., Kitchen, I., Winsky-Sommerer, R., Bailey, A., Bailey, A. Region-specific up-regulation of oxytocin receptor binding in the brain of mice following chronic nicotine administration. NEUROSCIENCE LETTERS 2015; 600(--):33-37. >>> Nicotine; SC; Mice; 2002; Controls received mp w/ saline; animal info (male, C57BL/6J); dependence;.

15256 Wu, Y., Song, P., Zhang, W.C., Liu, J.H., Dai, X.Y., Liu, Z.Y., Lu, Q.L., Ouyang, C.H., Xie, Z.L., Zhao, Z.X., Zhuo, X.Z., Viollet, B., Foretz, M., Wu, J.L., Yuan, Z.Y., Zou, M.H., Zou, M.H. Activation of AMPKalpha2 in adipocytes is essential for nicotine-induced insulin resistance in vivo. NATURE MEDICINE 2015; 21(--):373-+. >>> Nicotine; Saline; SC; Mice; rat; Controls received mp w/ vehicle; animal info (mice male, C57BL6J, 8 weeks old; rat male, Sprague Dawley, 10 weeks old); diabetes; long-term study;.

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6. Pentobarbital

5577 Kim, Y., Oh, S. Changes of the level of G protein alpha-subunit mRNA by tolerance to and withdrawal from pentobarbital in rats. Neurochemical Research 2002; 27(-6-):527-533. >>> Pentobarbital; Saline; CSF/CNS; Rat; 2001; Controls received mp w/ vehicle; tolerance; dependence; one week recovery period after cannula placement.

4418 Jang, C.-G., Oh, S., Zho, H., Ho, I.K. Autoradiography of [3H] glutamate binding during pentobarbital tolerance and withdrawal in the rat. Brain Research Bulletin 1999; 48(-1-):99-102. >>> Pentobarbital; Saline; CSF/CNS; Rat; 2ML1; Controls received mp with vehicle; tolerance; dependence; animals allowed one week recovery after cannula placement.

4291 Jang, C.-G., Oh, S., Ho, I.K. Changes in NMDAR2 subunit mRNA levels during pentobarbital tolerance/withdrawal in the rat brain: an in situ hybridization study. Neurochem. Res 1998; 23(-11-):1371-1377. >>> Pentobarbital; Saline; CSF/CNS; rat; 2ML1; controls received mp w/saline; tolerance.

15691 Oh, S., Wellman, S.E., Ho, I.K. Changes in (3H)forskolin binding to adenylate cyclase and (3H)phorbol dibutyrate binding to protein kinase c in pentobarbital tolerant/dependent rats. Neurochem. Res 1998; 23(-4-):463-467. >>> Pentobarbital; CSF/CNS; rat; 2ML1; guide cannula implanted; rats were allowed 1 week recovery before implantation of pump; tolerance; dependence.

4280 Oh, S., Wellman, S.E., Ho, I.K. Changes in (3H)forskolin binding to adenylate cyclase and (3H)phorbol dibutyrate binding to protein kinase c in pentobarbital tolerant/dependent rats. Neurochem. Res 1998; 23(-4-):463-467. >>> Pentobarbital; CSF/CNS; rat; 2ML1; guide cannula implanted; rats were allowed 1 week recovery before implantation of pump; tolerance; dependence.

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7. Phencyclidine

12876 Balla, A., Schneider, S., Sershen, H., Javitt, D.C. Effects of novel, high affinity glycine transport inhibitors on frontostriatal dopamine release in a rodent model of schizophrenia. European Neuropsychopharmacology 2012; 22(-12-):902-910. >>> Phencyclidine hydrochloride; Saline, sterile, physiological; SC; Rat; 2ML4; Control animals received mp w/ vehicle; animal info (Sprague Dawley, male, wks old, 160-200 g, 280-320 g).

10624 Pedersen, C.S., Goetghebeur, P., Dias, R. Chronic infusion of PCP via osmotic mini-pumps: A new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance. Journal of Neuroscience Methods 2009; 185(-1-):66-69. >>> Phencyclidine; SC; Rat; Controls received mp w/saline; animal info (Lister hooded, male); post op. care (Baitril, Rimadyl);"Using PCP mini-pump infusion instead of the well described intraperitoneal dosing bears the advantage of reducing the animal's stress levels, bypasses the risk of potential mis-dosing that could arise from multiple dosing events and consequently may reduce the number of animals needed."pg 69.

8040 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; 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.).

7188 Sams-Dodd, F. (+) MK-801 and phencyclidine induced neurotoxicity do not cause enduring behaviours resembling the positive and negative symptoms of schizophrenia in the rat. BASIC&CLINICAL PHARMACOLOGY&TOXICOLOGY 2004; 95(-5-):241-246. >>> MK-801; phencyclidine hydrochloride; Sodium chloride; SC; Rat; 2ML2; Controls received mp w/ vehicle; dose-response; comparison of SC injections vs. mp; post op. care (wound plast); NMDA antagonists.

6361 Balla, A., Sershen, H., Serra, M., Koneru, R., Javitt, D.C. Subchronic continuous phencyclidine administration potentiates amphetamine-induced frontal cortex dopamine release. Neuropsychopharmacology 2003; 28(-1-):34-44. >>> Phencyclidine, HCL; Saline, sterile physiological; SC; Rat; 2ML4; Controls received mp w/ vehicle; functionality of mp verified by serum PCP levels.

6073 Laurenzana, E.M., Gunnell, M.G., Gentry, W.B., Owens, S.M. Treatment of adverse effects of excessive phencyclidine exposure in rats with a minimal dose of monoclonal antibody. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-3-):1092-1098. >>> Phencyclidine; phencyclidine HCL;; Saline; sterile; SC; Rat; 2ML2; Controls received mp w/ vehicle; serum levels taken; good methods p. 1093; half-life (p. 1093) =3.9 h in rats; dependence; behavioral study.

5308 Balla, A., Hashim, A., Burch, S., Javitt, D.C., Lajtha, A., Sershen, H. Phencyclidine-induced dysregulation of dopamine response to amphetamine in prefrontal cortex and striatum. Neurochem. Res 2001; 26(-8-9-):1001-1006. >>> Phencyclidine HCl; Saline; SC; Rat; 2ML4; Controls received mp w/ vehicle; functionality of mp verified by PCP serum levels; NMDA antagonist.

5264 Jebelli, A.K., Doan, N., Ellison, G. Prenatal phencyclidine induces heightened neurodegeneration in rats in some brain regions, especially during 2nd trimester, but possible anti-apoptotic effects in others. Pharmacol Toxicol 2002; 90(--):20-25. >>> Phencyclidine; Saline; SC; rat (pregnant); 2ML1; controls received a saline pellet as a"sham minipump"; teratology.

5047 Balla, A., Koneru, R., Smiley, J., Sershen, H., Javitt, D.C. Continuous phencyclidine treatment induces schizophrenia-like hyperreactivity of striatal dopamine release. Neuropsychopharmacology 2001; 25(-2-):157-164. >>> Phencyclidine HCl; Saline, sterile; SC; rat; 2ML4; controls received mp w/ vehicle; functionality of mp verified by serum PCP levels; dose response (graphs p. 160); schizophrenia.

4926 Kyosseva, S.V., Owens, S., Elbein, A.D., Karson, C.N. Differential and region-specific activation of mitogen-activated protein kinases following chronic administration of phencyclidine in rat brain. Neuropsychopharmacology 2001; 24(--):267-277. >>> Phencyclidine HCl;; Saline;; SC;; rat;; 2ML2;; Controls received mp w/ vehicle; dose-response p. 270-271;.

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What researchers are saying ...

“We found recently that 21 d of treatment of rats with SSRIs, at clinically relevant and stable serum concentrations (achieved by the use of osmotic minipumps), caused robust downregulation of the SERT.”... “Studies on the effects of chronic antidepressants on the SERT have resulted in inconsistent reports (Owens and Nemeroff, 1998). Among the factors that may contribute to such inconsistency is the route of drug administration. In most studies of chronic administration of Ads to rats, the drugs are given intraperitoneally or subcutaneously, either once or twice daily. As rats metabolize these drugs more rapidly than humans, such dosage schedules can result in appreciable fluctuations in the serum concentration of drug throughout the day. For certain pharmacologic effects, sustained drug action may be needed” Benmansour et al. The Journal of Neuroscience 2002; 22(15):6766-6772.