Opposite Modulation of Cocaine-Seeking Behavior by D1- and D2-Like Dopamine Receptor Agonists

Activation of the mesolimbic dopamine system is known to trigger relapse in animal models of cocaine-seeking behavior. We found that this “priming” effect was selectively induced by D2-like, and not by D1-like, dopamine receptor agonists in rats. Moreover, D1-like receptor agonists prevented cocaine-seeking behavior induced by cocaine itself, whereas D2-like receptor agonists enhanced this behavior. These results demonstrate an important dissociation between D1- and D2-like receptor processes in cocaine-seeking behavior and support further evaluation of D1-like receptor agonists as a possible pharmacotherapy for cocaine addiction.

[1]  R. Belmaker,et al.  Haloperidol in Normals , 1977, British Journal of Psychiatry.

[2]  H. Fibiger,et al.  On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine , 1977, Pharmacology Biochemistry and Behavior.

[3]  J. Kebabian,et al.  Multiple receptors for dopamine , 1979, Nature.

[4]  H. Fibiger,et al.  Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens , 1980, Pharmacology Biochemistry and Behavior.

[5]  S H Snyder,et al.  Adenosine receptors and behavioral actions of methylxanthines. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Kebabian,et al.  Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor , 1981, Nature.

[7]  N. Goeders,et al.  Cortical dopaminergic involvement in cocaine reinforcement. , 1983, Science.

[8]  Jane Stewart,et al.  Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area , 1984, Pharmacology Biochemistry and Behavior.

[9]  P. Vezina,et al.  A comparison of the effects of intra-accumbens injections of amphetamine and morphine on reinstatement of heroin intravenous self-administration behavior , 1988, Brain Research.

[10]  G. Koob,et al.  Bromocriptine produces decreases in cocaine self-administration in the rat. , 1990, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[11]  K. Preston,et al.  Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers. , 1992, NIDA research monograph.

[12]  C. Gerfen,et al.  D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. , 1990, Science.

[13]  P. H. Andersen,et al.  Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy. , 1990, European journal of pharmacology.

[14]  F. Gawin.  Cocaine addiction: psychology and neurophysiology. , 1991, Science.

[15]  J. Witkin,et al.  Behavioral effects of selective dopaminergic compounds in rats discriminating cocaine injections. , 1991, The Journal of pharmacology and experimental therapeutics.

[16]  R. Spealman,et al.  Discriminative stimulus effects of cocaine in squirrel monkeys: involvement of dopamine receptor subtypes. , 1991, The Journal of pharmacology and experimental therapeutics.

[17]  S. Siris.  Diagnosis of secondary depression in schizophrenia: implications for DSM-IV. , 1991, Schizophrenia bulletin.

[18]  L. Stein,et al.  The D1 agonists SKF 82958 and SKF 77434 are self-administered by rats , 1992, Brain Research.

[19]  M. Martres,et al.  Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. Sibley,et al.  Molecular biology of dopamine receptors. , 1992, Trends in pharmacological sciences.

[21]  S. B. Caine,et al.  Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. , 1993, Science.

[22]  E. Nestler,et al.  Individual Differences in Locomotor Activity Are Associated with Levels of Tyrosine Hydroxylase and Neurofilament Proteins in the Ventral Tegmental Area of Sprague-Dawley Rats , 1993, Molecular and Cellular Neuroscience.

[23]  C. M. Stubbs,et al.  The dopamine D3 receptor: Chinese hamsters or Chinese whispers? , 1994, Trends in pharmacological sciences.

[24]  E. Nestler,et al.  Biochemical adaptations in the mesolimbic dopamine system in response to heroin self‐administration , 1995, Synapse.

[25]  A. Awad,et al.  Psychopharmacology: The Fourth Generation of Progress , 1998, CNS Spectrums.