Cortical dopaminergic involvement in cocaine reinforcement.

Neuronal systems involved in the initiation of cocaine reinforcement were investigated by identifying brain sites where direct application of the drug was reinforcing. This was accomplished by allowing rats to self-administer picomolar concentrations of cocaine into discrete brain regions. The medial prefrontal cortex supported self-administration, while the nucleus accumbens and ventral tegmental area did not. Self-administration could be attenuated by including equimolar concentrations of the dopaminergic D2-receptor antagonist sulpiride in the microinjection system. These results imply that cocaine reinforcement is mediated in part through a direct action on mesocortical dopaminergic receptors.

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

[2]  R. Wise Action of drugs of abuse on brain reward systems , 1980, Pharmacology Biochemistry and Behavior.

[3]  S. Z. Langer,et al.  The potentiation of responses to adrenergic nerve stimulation in the presence of cocaine: its relationship to the metabolic fate of released norepinephrine. , 1974, The Journal of pharmacology and experimental therapeutics.

[4]  M. Hadfield,et al.  Cocaine: effect of in vivo administration on synaptosomal uptake of norepinephrine. , 1980, Biochemical pharmacology.

[5]  P. Spano,et al.  Sulpiride: a study of the effects on dopamine receptors in rat neostriatum and limbic forebrain. , 1975, Life sciences.

[6]  R. Wise,et al.  Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine or phenoxybenzamine. , 1977, Canadian journal of psychology.

[7]  T. Thompson,et al.  Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. , 1968, The Journal of pharmacology and experimental therapeutics.

[8]  R. T. Kelleher,et al.  Behavior controlled by scheduled injections of cocaine in squirrel and rhesus monkeys. , 1976, Journal of the experimental analysis of behavior.

[9]  Michael A. Bozarth,et al.  Electrolytic microinfusion transducer system: an alternative method of intracranial drug application , 1980, Journal of Neuroscience Methods.

[10]  E. Rolls,et al.  Intracerebral self-administration of amphetamine by rhesus monkeys , 1981, Neuroscience Letters.

[11]  J. Woods,et al.  Codeine- and cocaine-reinforced responding in rhesus monkeys: effects of dose on response rates under a fixed-ratio schedule. , 1974, The Journal of pharmacology and experimental therapeutics.

[12]  R. Wise Catecholamine theories of reward: A critical review , 1978, Brain Research.

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

[14]  G. Koob,et al.  Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats , 1982, Pharmacology Biochemistry and Behavior.

[15]  H. Fibiger,et al.  Ascending projections of presumed dopamine-containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase , 1977, Neuroscience.

[16]  O. Lindvall,et al.  Distribution of putative neurotransmitters in the neocortex , 1979, Neuroscience.

[17]  C. Schuster,et al.  Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. , 1973, Journal of the experimental analysis of behavior.

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

[19]  J. Rotrosen,et al.  EFFECTS OF ACUTE COCAINE TREATMENT ON THE TURNOVER OF 5‐HYDROXYTRYPTAMINE IN THE RAT BRAIN , 1975, British journal of pharmacology.

[20]  S. Freedman,et al.  [3H]Sulpiride, a ligand for neuroleptic receptors. , 1981, Neuropharmacology.