Skip to main content
SpringerLink
Log in

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ator NA, Griffiths RR (1985) Lorazepam and pentobarbital discrimination: interactions with CGS 8216 and caffeine. Eur J Pharmacol 107:169–181

    Google Scholar 

  • Ator NA, Griffiths RR (1986) Discriminative stimulus effects of atypical anxiolytics in baboons and rats. J Pharmacol Exp Ther 237:393–403

    Google Scholar 

  • Biel JH (1970) Structure-activity relationships of amphetamine and derivatives. In: Amphetamines and Related compounds. Costa E, Garattini S (eds) Raven Press, New York, pp 3–19

    Google Scholar 

  • Brogden RN, Heel RC, Speight TM, Avery GS (1979) Nomifensine: a review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs 18:1–24

    Google Scholar 

  • Chan M-Y, Ehsanullah R, Wadsworth J, McEwen J (1980) A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects. Br J Clin Pharmac 9:247–253

    Google Scholar 

  • Colpaert FC, Niemegeers CJE, Janssen PAJ (1979) Discriminative stimulus properties of cocaine: neuropharmacological characteristics as derived from stimulus generalization experiments. Pharmacol Biochem Behav 10:535–546

    Google Scholar 

  • Deneau G, Yanagita G, Seevers MH (1969) Self-administration of psychoactive substances by the monkey: a measure of psychological dependence. Psychopharmacologia 16:30–48

    Google Scholar 

  • Dufrensne RL, Becker RE, Blitzer R, Wagner RL, Lal H (1985) Safety and efficacy of bupropion, a novel antidepressant. Drug Dev Res 6:39–45

    Google Scholar 

  • Ferris RM, White HL, Cooper BR, Maxwell A, Tang FLM, Beaman OJ, Russell A (1981) Some neurochemical properties of a new antidepressant, bupropion hydrochloride (Wellbutrin™). Drug Dev Res 1:21–35

    Google Scholar 

  • Findley JD, Robinson WW, Peregrino L (1972) Addiction to secobarbital and chloridazepoxide in the rhesus monkey by means of a self-infusion preference procedure. Pyschopharmacology 78:204–209

    Google Scholar 

  • Fischman MW, Schuster CR, Resnekov L, Shick JFE, Krasnegor NA, Fennell W, Freedman D (1976) Cardiovascular and subjective effects of intravenous cocaine administration in humans. Arch Gen Psychiatry 33:983–989

    Google Scholar 

  • Gentili P, de Maria F, de Vanna M, Drago F, Omer LMO, Ismail S (1984) Diclofensine in the treatment of depressed geriatric hospitalized patients: a placebo-controlled double-blind rial. Cur Ther Res 35[3]:386–395

    Google Scholar 

  • Griffith JD (1966) A study of illicit amphetamine drug traffic in Oklahoma City. Am J Psychiatry 123:561–569

    Google Scholar 

  • Griffith JD, Nutt JG, Jasinski DR (1975) A comparison of fenfluramine and amphetamine in man. Clin Pharmacol Ther 18:563–570

    Google Scholar 

  • Griffiths RR, Winger G, Brady JV, Snell JD (1976) Comparison of behavior maintained by infusions of eight phenylethylamines in baboons. Psychopharmacology 50:251–258

    Google Scholar 

  • Griffiths RR, Brady JV, Snell JD (1978) Relationship between anorectic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability. Biol Psychiat 13:283–290

    Google Scholar 

  • Griffiths RR, Brady JV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures: psychomotor stimulants and hallucinogens. In: Thompson T, Dews PB (eds) Advances in Behavioral Pharmacology, vol 2. Academic Press, NY, pp 164–208

    Google Scholar 

  • Hamilton MJ, Smith PR, Peck AW (1983) Effects of bupropion, nomifensine and dexamphetamine on performance, subjective feelings, autonomic variables and electroencephalogram in healthy volunteers. Br J Clin Pharmacol 15:367–374

    Google Scholar 

  • Hindmarch I, Parrott AC (1977) Repeated dose comparison of nomifensine, imipramine and placebo on subjective assessments of sleep and objective measures of psychomotor performance. Br J Clin Pharmacol 4 [Suppl 2] 167s-173s

    Google Scholar 

  • Hoffmeister F, Goldberg SR (1973) A comparison of chlorpromazine, imipramine, morphine,d-amphetamine self-administration in cocaine-dependent rhesus monkeys. J Pharmacol Exp Ther 187:8–14

    Google Scholar 

  • Houlihan WJ, Babington RG (1979) Anorexigenics In: Wolff ME (ed) Burger's Medicinal Chemistry. Wiley, New York, pp 1069–1108

    Google Scholar 

  • Huang J-T, Ho BT (1974) Discriminative stimulus properties ofd-amphetamine and related compounds in rats. Pharmacol Biochem Behav 2:669–673

    Google Scholar 

  • Johanson CE (1986) Stimulant depressant Harris LS (ed) report. In: Problems of drug dependence 1985. NIDA Res Monogr No. 67, US Government Printing Office, (ADM) 86-1448, pp 98–104

  • Jones CN, Howard JL, McBennett ST (1980) Stimulus properties of antidepressants in the rat. Psychopharmacology 67:111–118

    Google Scholar 

  • Katz RJ, Baldrighi G, Carroll BJ (1977) Effects of nomifensine (HOE 984) upon psychomotor activity, intracranial self-stimulation in the rat. Pharmacol Biochem Behav 7:269–272

    Google Scholar 

  • Keller HH, Schaffner R, Carruba MO, Burkard WP, Pieri M, Bonetti EP, Scherschlicht R, Da Pradam, Haefely WE, (1982), Diclofensine (Ro 8-4650) — A potent inhibitor of monoamine uptake: biochemical and behavioural effects in comparison with nomifensine. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: molecular mechanisms. Raven Press, New York, pp 249–263

    Google Scholar 

  • Kennedy LT, Hanbauer I (1983) Sodium-sensitive cocaine binding to rat striatal membrane: Possible relationship to dopamine uptake sites. J Neurochem 41:172–178

    Google Scholar 

  • Koe BK (1976) Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparation of rat brain. J Pharmacol Exp Ther 199:649–661

    Google Scholar 

  • Kramer JG, Fischman VS, Littlefield DC (1967) Amphetamine abuse: pattern and effects of high doses taken intravenously. JAMA 201:305–309

    Google Scholar 

  • Kruse H, Hoffman I, Gerhards HJ, Levin M, Schacht U (1977) Pharmacological and biochemical studies with three metabolites of nomifensine. Psychopharmacology 51:117–123

    Google Scholar 

  • Lukas SE, Griffiths RR, Bradford LD, Brady JV, Daley L, DeLorenzo R (1982) A tethering system for intravenous and intragastric drug administration in the baboon. Pharmacol Biochem Behav 17:823–829

    Google Scholar 

  • Martin WR, Sloan JW, Sapira JD, Jasinsyki DR (1971) Physiologic, subjective, and behavioral effects of amphetamine and methamphetamine, ephedrine, phenmetrazine and methylphenidate in man. Clin Pharmacol Ther 12:245–258

    Google Scholar 

  • McKearney JW (1982) Effects of dopamine uptake inhibitors on schedule-controlled behavior in the squirrel monkey. Psychopharmacology 78:377–379

    Google Scholar 

  • Miller L, Griffith J (1983) A comparison of bupropion, dextroam-phetamine, and placebo in mixed-substance abusers. Psychopharmacology 80:199–205

    Google Scholar 

  • Omer OLM, Díaz-Olivera M, Ismail S (1984) Therapeutic efficacy, tolerance of diclofensine in psychoreactive depression — a double-blind comparison with placebo. Methods, Find Exp Clin Pharmacol 6:146–151

    Google Scholar 

  • Peck AW, Bye CE, Clubley M, Henson T, Riddington C (1979) A comparison of bupropion hydrochloride with dexamphetamine and amitriptyline in healthy subjects. Br J clin Pharmacol 7:469–478

    Google Scholar 

  • Pickens R, Harris WC (1968) Self-administration ofd-amphetamine by rats. Psychopharmacologia 12:158–163

    Google Scholar 

  • Rastogi SK, McMillan DE (1985) Effects of some typical and atypical antidepressants on schedule-controlled responding in rats. Drug Dev Res 5:243–250

    Google Scholar 

  • Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters appear related to drug self-administration. Science 237:1219–1223

    Google Scholar 

  • Soroko FE, Mehta NB, Maxwell RA, Fems RM, Schroeder DH (1977) Bupropion hydrochloride (±) α-t-butylamino-3-chloropropiophenone HCl): a novel antidepressant agent. J Pharm Pharmacol 29:767–770

    Google Scholar 

  • Spyraki C, Fibiger HC (1981) Intravenous self-administration of nomifensine in rats: implications for abuse potential in humans. Science 212:1167–1168

    Google Scholar 

  • Wilcoxon F (1945) Individual comparisons by ranking methods. Biometrics Bull 1:80–83

    Google Scholar 

  • Wilson MC, Buelke J (1978) Discriminative properties ofl-amphetamine: stimulus generalization, In: Drug discrimination and state dependent learning. Ho BT, Richards DW, Chute DL (eds) Academic Press, New York, pp 47–77

    Google Scholar 

  • Winger G, Woods JH (1985) Comparison of fixed-ratio and progressive ratio schedules of maintenance of stimulant drug-reinforced responding. Drug Alcohol Depend 15:123–130

    Google Scholar 

  • Wittenborn JR, Flaherty CF, McGough E, Bossange KA, Nash RJ (1976) A comparison of the effect of imipramine, nomifensine, placebo on the psychomotor performance of normal males. Psychopharmacology 51:85–90

    Google Scholar 

  • Woods JH, Katz JL, Medzihrandsky F, Smith CB, Winger GD (1983) Evaluation of new compounds for opioid activity: 1982. annual report. In: Harris LS (ed) Problems of drug dependence 1982. NIDA Res Monogr No. 43, US Government Printing Office, (ADM) 83-1264, pp 457–511

  • Woods JH, Tessel RE (1974) Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey. Science 185:1067–1069

    Google Scholar 

  • Yanagita T, Wakasa Y, Oinumam N (1981) The dependence potential of nomifensine tested in rhesus monkeys. CIEA Preclin Rep 7:101–113

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Division of Behavioral Biology, The Johns Hopkins University School of Medicine, 21225, Baltimore, MD, USA

    R. J. Lamb & Roland R. Griffiths

Authors
  1. R. J. Lamb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roland R. Griffiths
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamb, R.J., Griffiths, R.R. Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine. Psychopharmacology 102, 183–190 (1990). https://doi.org/10.1007/BF02245920

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245920

Key words

Search

Navigation