Abstract
We investigated the ability of dopamine D1 and D2 class receptor antagonists to prevent the induction of behavioral sensitization to cocaine. The D2 receptor antagonist eticlopride failed to prevent the induction of cocaine sensitization. An intermediate dose of the D1 receptor antagonist SCH 23390 (0.1 mg/kg) appeared to prevent the induction of cocaine sensitization when tested after 3 days of withdrawal, but sensitization was clearly evident after 10 days of withdrawal. High doses of SCH 23390 alone produced supersensitivity to the behavioral effects of cocaine and to the inhibitory effects of D1 receptor agonists on nucleus accumbens neurons. Co-administration of eticlopride and SCH 23390 also failed to prevent the induction of cocaine sensitization. SCH 23390, but not eticlopride, prevented the expression of cocaine sensitization. We conclude that dopamine receptors are either not involved in the induction of cocaine sensitization or that redundant mechanisms exist to produce the same neuroadaptations.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Badiani A, Browman KE, Robinson TE . (1995): Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine. Brain Res 674: 291–298
Beninger RJ, Herz RS . (1986): Pimozide blocks establishment but not expression of cocaine-induced environment-specific conditioning. Life Sci 38: 1425–1431
Bjijou Y, Stinus L, Le Moal M, Cador M . (1996): Evidence for selective involvement of dopamine D1 receptors of the ventral tegmental area in the behavioral sensitization induced by intra-ventral tegmental area injections of D-amphetamine. J Pharmacol Exp Ther 277: 1177–1187
Bradberry CW . (1994): Microdialysis assessment of the impact of (+)3,4-methylenedioxymethamphetamine, cocaine, and cocaethylene on serotonergic neurons. Drug Dev Res 33: 1–9
Cass WA, Zahniser NR . (1993): Cocaine levels in striatum and nucleus accumbens: Augmentation following challenge injection in rats withdrawn from repeated cocaine administration. Neurosci Lett 152: 177–180
Cervo L, Samanin R . (1996): Effects of dopaminergic and glutamatergic receptor antagonists on the establishment and expression of conditioned locomotion to cocaine in rats. Brain Res 731: 31–38
Creese I, Chen A . (1985): Selective D-1 dopamine receptor increase following chronic treatment with SCH 23390. Eur J Pharmacol 109: 127–128
Essman WD, Singh A, Lucki I . (1994): Serotonergic properties of cocaine: Effects on a 5-HT2 receptor-mediated behavior and on extracellular concentrations of serotonin and dopamine. Pharmacol Biochem Behav 49: 107–113
Fontana D, Post RM, Weiss SRB, Pert A . (1993): The role of D1- and D2-dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior. Behav Pharmacol 4: 375–387
Hamamura T, Akiyama K, Akimoto K, Kashihara K, Okumura K, Ujike H, Otsuki S . (1991): Co-administration of either a selective D1 or D2 dopamine antagonist with amphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis. Brain Res 546: 40–46
Heidbreder CA, Thompson AC, Shippenberg TS . (1996): Role of extracellular dopamine in the initiation and long-term expression of behavioral sensitization to cocaine. J Pharmacol Exp Ther 278: 490–502
Henry DJ, Greene MA, White FJ . (1989): Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: repeated administration. J Pharmacol Exp Ther 251: 833–839
Henry DJ, White FJ . (1991): Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens. J Pharmacol Exp Ther 258: 882–890
Henry DJ, White FJ . (1995): The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons. J Neurosci 15: 6287–6299
Hu X-T, White FJ . (1994): Loss of D1/D2 dopamine receptor synergisms following repeated administration of D1 or D2 receptor selective antagonists: Electrophysiological and behavioral studies. Synapse 17: 43–61
Kalivas PW . (1995): Neural basis of behavioral sensitization to cocaine. In Hammer RP, Jr (ed), The Neurobiology of Cocaine: Cellular and Molecular Mechanisms. Boca Raton, FL, CRC Press, pp 81–98
Kalivas PW, Duffy P . (1993): Time course of extracellular dopamine and behavioral sensitization to cocaine. I. Dopamine axon terminals. J Neurosci 13: 266–275
Kalivas PW, Stewart J . (1991): Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16: 223–224
Karler R, Calder LD, Chaudhry IA, Turkanis SA . (1989): Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801. Life Sci 45: 599–606
Karler R, Calder LD, Bedingfield JB . (1994): Cocaine behavioral sensitization and the excitatory amino acids. Psychopharmacology (Berl) 115: 305–310
Koeltzow TE, Joshi A, Hu X-T, Wolf ME, White FJ . (1997): Dopamine receptor antagonists and the induction of sensitization to cocaine and amphetamine. Soc Neurosci Abst 23 (in press).
Koob GF . (1992): Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13: 177–184
Kuczenski R, Leith NJ . (1981): Chronic amphetamine: Is dopamine a link in or a mediator of the development of tolerance and reverse tolerance? Pharmacol Biochem Behav 15: 405–413
Kuczenski R, Segal DS . (1989): Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci 9: 2051–2065
Kuribara H . (1995a): Dopamine D1 receptor antagonist SCH 23390 retards methamphetamine sensitization in both combined administration and early posttreatment schedules in mice. Pharmacol Biochem Behav 52: 759–763
Kuribara H . (1995b): Modification of cocaine sensitization by dopamine D1 and D2 receptor antagonists in terms of ambulation in mice. Pharmacol Biochem Behav 51: 799–805
Kuribara H . (1995c): Inhibition of methamphetamine sensitization by post-methamphetamine treatment with SCH 23390 or haloperidol. Psychopharmacology (Berl) 119: 34–38
Kuribara H, Uchihashi Y . (1993): Dopamine antagonists can inhibit methamphetamine sensitization, but not cocaine sensitization, when assessed by ambulatory activity in mice. J Pharm Pharmacol 45: 1042–1045
Kuribara H, Uchihashi Y . (1994): Effects of dopamine antagonism on methamphetamine sensitization: Evaluation by ambulatory activity in mice. Pharmacol Biochem Behav 47: 101–106
Martin-Iverson MT, Reimer AR . (1994): Effects of nimodipine and/or haloperidol on the expression of conditioned locomotion and sensitization to cocaine in rats. Psychopharmacology (Berl) 114: 315–320
Mattingly BA, Hart TC, Lim K, Perkins C . (1994): Selective antagonism of dopamine D1 and D2 receptors does not block the development of behavioral sensitization to cocaine. Psychopharmacology (Berl) 114: 239–242
Mattingly BA, Rowlett JK, Ellison T, Rase K . (1996): Cocaine-induced behavioral sensitization: Effects of haloperidol and SCH 23390 treatments. Pharmacol Biochem Behav 53: 481–486
McCreary AC, Marsden CA . (1993): Cocaine-induced behaviour: Dopamine D1 receptor antagonism by SCH 23390 prevents expression of conditioned sensitisation following repeated administration of cocaine. Neuropharmacology 32: 387–391
McGonigle P, Boyson SJ, Reuter S, Molinoff PB . (1989): Effects of chronic treatment with selective and nonselective antagonists on the subtypes of dopamine receptors. Synapse 3: 74–82
Parsons LH, Koob GF, Weiss F . (1995): Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine. J Pharmacol Exp Ther 274: 1182–1191
Pettit HO, Pan H-T, Parsons LH, Justice JB, Jr . (1990): Extracellular concentrations of cocaine and dopamine are enhanced during chronic cocaine administration. J Neurochem 55: 798–804
Post RM . (1980): Intermittent versus continuous stimulation: Effect of time interval on the development of sensitization or tolerance. Life Sci 26: 1275–1282
Post RM, Weiss SRB, Pert A . (1992): Sensitization and kindling effects of chronic cocaine administration. In Lakoski JM, Galloway MP, White FJ (eds), Cocaine: Pharmacology, Physiology and Clinical Strategies. Boca Raton, FL, CRC Press, pp 115–161
Post RM, Contel NR . (1983): Human and animal studies of cocaine: Implications for development of behavioral pathology. In Creese I (ed), Stimulants: Neurochemical, Behavioral and Clinical Perspectives. New York, Raven Press, pp 169–203
Reimer AR, Martin-Iverson MT . (1994): Nimodipine and haloperidol attenuate behavioral sensitization to cocaine but only nimodipine blocks the establishment of conditioned locomotion by cocaine. Psychopharmacology 113: 404–410
Reith MEA, Benuck M, Lajtha A . (1987): Cocaine disposition in the brain after continuous or intermittent treatment and locomotor stimulation in mice. J Pharmacol Exp Ther 243: 281–287
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ . (1987): Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237: 1219–1223
Robinson TE, Becker JB . (1986): Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis. Brain Res Rev 11: 157–198
Robinson TE, Berridge KC . (1993): The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain Res Rev 18: 247–291
Self DW, Nestler EJ . (1995): Molecular mechanisms of drug reinforcement and addiction. Annu Rev Neurosci 18: 463–495
Shippenberg TS, Heidbreder C . (1995): Sensitization to the conditioned rewarding effects of cocaine: Pharmacological and temporal characteristics. J Pharmacol Exp Ther 273: 808–815
Stewart J, Badiani A . (1993): Tolerance and sensitization to the behavioral effects of drugs. Behav Pharmacol 4: 289–312
Stewart J, Vezina P . (1989): Microinjections of SCH 23390 into the ventral tegmental area and substantia nigra pars reticulata attenuate the development of sensitization to the locomotor activating effects of systemic amphetamine. Brain Res 495: 401–406
Tella SR . (1994): Differential blockade of chronic versus acute effects of intravenous cocaine by dopamine receptor antagonists. Pharmacol Biochem Behav 48: 151–159
Tella SR . (1996): Possible novel pharmacodynamic action of cocaine: Cardiovascular and behavioral evidence. Pharmacol Biochem Behav 54: 343–354
Ujike H, Onoue T, Akiyama K, Hamamura T, Otsuki S . (1989): Effects of selective D-1 and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization. Psychopharmacology 98: 89–92
Ujike H, Kuroda S, Otsuki S . (1996): σ receptor antagonists block the development of sensitization to cocaine. Eur J Pharmacol 296: 123–128
Ushijima I, Carino MA, Horita A . (1995): Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats. Pharmacol Biochem Behav 52: 737–741
Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli O . (1991): Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350: 610–614
Vezina P . (1996): D1 dopamine receptor activation is necessary for the induction of sensitization by amphetamine in the ventral tegmental area. J Neurosci 16: 2411–2420
Vezina P, Stewart J . (1989): The effect of dopamine receptor blockade on the development of sensitization to the locomotor activating effects of amphetamine and morphine. Brain Res 499: 108–120
Waddington JL, Daly SA . (1993): Regulation of unconditioned motor behaviour by D1:D2 interactions. In Waddington JL (ed), D1:D2 Dopamine Receptor Interactions. San Diego, CA, Academic Press, pp 51–78
Weiss F, Paulus MP, Lorang MT, Koob GF . (1992): Increases in extracellular dopamine in the nucleus accumbens by cocaine are inversely related to basal levels: Effects of acute and repeated administration. J Neurosci 12: 4372–4380
Weiss SRB, Post RM, Pert A, Woodward R, Murman D . (1989): Context-dependent cocaine sensitization: Differential effect of haloperidol on development versus expression. Pharmacol Biochem Behav 34: 655–661
White FJ, Hu X-T, Henry DJ . (1993): Electrophysiological effects of cocaine in the rat nucleus accumbens: Microiontophoretic studies. J Pharmacol Exp Ther 266: 1075–1084
White FJ, Hu X-T, Henry DJ, Zhang X-F . (1995a): Neurophysiological alterations in the mesocorticolimbic dopamine system during repeated cocaine administration. In Hammer RP Jr (ed), The Neurobiology of Cocaine: Cellular and Molecular Mechanisms. Boca Raton, FL, CRC Press, pp 95–115
White FJ, Hu X-T, Zhang X-F, Wolf ME . (1995b): Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. J Pharmacol Exp Ther 273: 445–454
White FJ . (1996): Synaptic regulation of mesocorticolimbic dopamine neurons. Annu Rev Neurosci 19: 405–436
White FJ, Hu X-T, Zhang X-F . (1998): Neuroadaptations in nucleus accumbens neurons resulting from repeated cocaine administration. In Goldstein D, Eisenhofer G, McCarty R (eds), Catecholamines: Bridging Basic Science with Clinical Medicine. San Diego, CA, Academic Press, pp. 1006–1009
White FJ, Hu X-T . (1993): Electrophysiological correlates of D1:D2 interactions. In Waddington JL (ed), D1:D2 Dopamine Receptor Interactions. San Diego, CA, Academic Press, pp 79–114
White FJ, Wolf ME . (1991): Psychomotor stimulants. In Pratt JA (ed), The Biological Basis of Drug Tolerance and Dependence. London, Academic Press, pp 153–197
Wise RA, Bozarth MA . (1987): A psychomotor stimulant theory of addiction. Psychol Rev 94: 469–492
Wolf ME, Jeziorski M . (1993): Coadministration of MK-801 with amphetamine, cocaine or morphine prevents rather than transiently masks the development of behavioral sensitization. Brain Res 613: 291–294
Acknowledgements
We thank Pamela Alvarez and Lorinda Baker for technical assistance, and Dr. M.E. Wolf for helpful comments and suggestions. This work was supported by USPHS Grant DA04093 from the National Institute on Drug Abuse (NIDA). FJW is also the recipient of a NIDA Research Scientist Development Award (DA00207).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
White, F., Joshi, A., Koeltzow, T. et al. Dopamine Receptor Antagonists Fail to Prevent Induction of Cocaine Sensitization. Neuropsychopharmacol 18, 26–40 (1998). https://doi.org/10.1016/S0893-133X(97)00093-6
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1016/S0893-133X(97)00093-6
Keywords
This article is cited by
-
Cocaine restricts nucleus accumbens feedforward drive through a monoamine-independent mechanism
Neuropsychopharmacology (2022)
-
Importance of dopaminergic neurotransmission for the RU 24969–induced locomotor activity of male and female rats during the preweanling period
Naunyn-Schmiedeberg's Archives of Pharmacology (2021)
-
Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens
Molecular Psychiatry (2020)
-
Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.
Psychopharmacology (2017)
-
Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats
Psychopharmacology (2016)


