Skip to main content
SpringerLink
Log in

Bromocriptine self-administration and bromocriptine-reinstatement of cocaine-trained and heroin-trained lever pressing in rats

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

Abstract

Rats were trained to lever press for intravenous cocaine (1.0 mg/kg/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg/kg/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg/kg/injection) or heroin (0.1 mg/kg/injection) reinforcement; drug was available for the first 2 h of each daily session; saline was substituted for cocaine or heroin for 5 subsequent hours. One hour into each saline substitution session, an intravenous injection of saline or bromocriptine (0.0, 0.5, 1.0, or 2.0 mg/kg) was given. Bromocriptine reinstated both cocaine-trained and herointrained lever pressing; under these conditions, the drug was most effective in the heroin-trained animals. Reinforcing doses of clonidine (0.0625 and 0.125 mg/kg), methohexital, and nicotine (0.05 and 0.1 mg/kg), and a sub-intoxicating dose of ethanol (2 g/kg) failed to reinstate cocaine-trained responding. These data indicate that bromocriptine has cocaine-like and heroin-like stimulus and reinforcing effects.

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

Access this article

Log in via an institution

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

  • Acguas E, Carboni E, Leone P, Di Chiara G (1989) SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade? Psychopharmacology 99:151–155

    Google Scholar 

  • Brown ZW, Amit Z, Weeks JR (1976) Simple flow-thru swivel for infusions into unrestrained animals. Pharmacol Biochem Behav 5:363–365

    Google Scholar 

  • Clarke PBS, Kumar R (1983) The effects of nicotine on locomotor activity in non-tolerant and tolerant rats. Br J Pharmacol 78:329–337

    Google Scholar 

  • Collins RJ, Weeks JR, Cooper MM, Good PI, Russell RR (1984) Prediction of abuse liability of drugs using IV self-administration by rats. Psychopharmacology 82:6–13

    Google Scholar 

  • Dackis CA, Gold MS (1985a) Bromocriptine as treatment of cocaine abuse. Lancet I:1151–1152

    Google Scholar 

  • Dackis CA, Gold MS (1985b) New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 9:469–477

    Google Scholar 

  • Davis WM, Smith SG (1975) Effect of haloperidol on (+)-amphetamine self-administration. J Pharm Pharmacol 27:540–542

    Google Scholar 

  • Davis WM, Smith SG (1977) Catecholaminergic mechanisms of reinforcement: direct assessment by drug self-administration. Life Sci 20:483–492

    Google Scholar 

  • de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143

    Google Scholar 

  • de Wit H, Stewart J (1983) Drug reinstatement of heroin-reinforced responding in the rat. Psychopharmacology 79:29–31

    Google Scholar 

  • de Wit H, Wise RA (1977) Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide but not with the noradrenergic blockers phentolamine or phenoxybenzamine. Can J Psychol 31:195–203

    Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs of abuse preferentially stimulate dopamine release in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278

    Google Scholar 

  • Di Mascio A, Havens LL, Klerman GL (1963) The psychopharmacology of phenothiazine compounds: a comparative study of the effects of chlorpromazine, promethazine, trifluoperazine, and perphenazine in normal males. 2. Results and discussion. J Nerv Ment Dis 136:168–186

    Google Scholar 

  • Dougherty J, Miller D, Todd G, Kostenbauder HB (1981) Reinforcing and other behavioral effects of nicotine. Neurosci Biobehav Rev 5:487–495

    Google Scholar 

  • Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacology 78:204–209

    Google Scholar 

  • Fibiger HC (1978) Drugs and reinforcement mechanisms: a critical review of the catecholamine theory. Ann Rev Pharmacol Toxicol 18:37–56

    Google Scholar 

  • Gerber GJ, Stretch R (1975) Drug-induced reinstatement of extinguished self-administration behavior in monkeys. Pharmacol Biochem Behav 3:1055–1061

    Google Scholar 

  • Gerhardt GA, Pang K, Rose GM (1987) In vivo electrochemical demonstration of the presynaptic actions of phencyclidine in rat caudate nucleus. J Pharmacol Exp Ther 241:714–721

    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. Academic Press, New York, pp 163–208

    Google Scholar 

  • Heikkila RE, Orlansky H, Cohen G (1975) Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices. Biochem Pharmacol 24:847–852

    Google Scholar 

  • Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989) Cocaine-induced cocaine craving. Psychopharmacology 97:59–64

    Google Scholar 

  • Markstein R (1981) Neurochemical effects of some ergot derivatives: a basis for their antiparkinson effects. J Neural Transm 51:39–59

    Google Scholar 

  • Matthews RT, German DC (1984) Electrophysiological evidence for excitation of rat ventral tegmental area dopaminergic neurons by morphine. Neuroscience 11:617–626

    Google Scholar 

  • Numan R (1981) Multiple exposures to ethanol facilitate intravenous self-administration of ethanol by rats. Pharmacol Biochem Behav 15:101–108

    Google Scholar 

  • Ostrowski NL, Hatfield CB, Caggiula AR (1982) The effects of low doses of morphine on the activity of dopamine containing cells and on behavior. Life Sci 31:2347–2350

    Google Scholar 

  • Pickens R, Thompson T (1968) Cocaine-reinforced behavior in rats: Effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther 161:122–129

    Google Scholar 

  • Pickens R, Muchow D, DeNoble V (1981) Methohexital-reinforced responding in rats: Effects of fixed ratio size and injection dose. J Pharmacol Exp Ther 216:205–209

    Google Scholar 

  • Risner ME, Jones BE (1980) Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology 71:83–89

    Google Scholar 

  • Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620

    Google Scholar 

  • Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-OHDA lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787

    Google Scholar 

  • Stewart J (1983) Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug self-administration. Progress in Neuropsychopharmacol Biol Psychiatr 7:591–597

    Google Scholar 

  • Stewart J (1984) Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area. Pharmacol Biochem Behav 20:917–923

    Google Scholar 

  • Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215–247

    Google Scholar 

  • Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–87

    Google Scholar 

  • Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263

    Google Scholar 

  • Wise RA (1988) The neurobiology of craving: implications for the understanding and treatment of addiction. J Abnorm Psychol 97:118–132

    Google Scholar 

  • Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492

    Google Scholar 

  • Wise RA, Rompré P-P (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225

    Google Scholar 

  • Wise RA, Yokel RA, de Wit H (1976) Both positive reinforcement and conditioned taste aversion from amphetamine and from apomorphine in rats. Science 191:1273–1274

    Google Scholar 

  • Woolverton WL, Goldberg LI, Ginos J (1984) Intravenous self-administration of dopamine receptor agonists by rhesus monkeys. J Pharmacol Exp Ther 230:678–683

    Google Scholar 

  • Yokel RA, Pickens R (1974) Drug level ofd- andl-amphetamine during intravenous self-administration. Psychopharmacologia 43:255–264

    Google Scholar 

  • Yokel RA, Pickens R (1976) Extinction responding following amphetamine self-administration: determination of reinforcement magnitude. Physiol Psychol 4:39–42

    Google Scholar 

  • Yokel RA, Wise RA (1975) Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549

    Google Scholar 

  • Yokel RA, Wise RA (1976) Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48:311–318

    Google Scholar 

  • Yokel RA, Wise RA (1978) Amphetamine-type reinforcement by dopamine agonists in the rat. Psychopharmacology 58:289–296

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, H3G 1M8, Montreal, Canada

    R. A. Wise & A. Murray

  2. Department of Psychology, State University of New York, 14260, Buffalo, NY, USA

    M. A. Bozarth

Authors
  1. R. A. Wise
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Murray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. A. Bozarth
    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

Wise, R.A., Murray, A. & Bozarth, M.A. Bromocriptine self-administration and bromocriptine-reinstatement of cocaine-trained and heroin-trained lever pressing in rats. Psychopharmacology 100, 355–360 (1990). https://doi.org/10.1007/BF02244606

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244606

Key words

Search

Navigation