Neuropharmacological assessment of cocaine self-administration into the medial prefrontal cortex.
Neuronal systems involved in the initiation of reinforcement following the response-contingent delivery of cocaine into the medial prefrontal cortex were investigated. Dose-effect analyses demonstrated that different concentrations of cocaine result in distinguishable patterns of self-administration which could be empirically determined by measuring the relative frequency distribution of the interinfusion intervals. The substitution of equimolar d-amphetamine or lidocaine resulted in rates and patterns of responding similar to vehicle or a low dose of cocaine, suggesting that reinforcement occurs from actions on specific receptors rather than through a local anesthetic neuronal blockade or through properties of a general psychomotor stimulant. The co-infusion of equimolar concentrations of sulpiride attenuated intake and produced patterns of responding similar to those seen after decreasing the cocaine dose consistent with an excitatory role for D2 dopaminergic receptors in these processes. Sulpiride and cocaine may act at separate sites since the decreased intake was not reversed by increasing the concentration of cocaine. D1 dopaminergic, muscarinic-cholinergic and beta-noradrenergic receptor antagonists either did not modulate drug-intake or had minimal effects. Cocaine reinforcement may result in part from an activation of D2 receptors initiating neuronal activity in pathways or circuits mediating reinforcement processes.
Goeders
N E
NE
Dworkin
S I
SI
Smith
J E
JE
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007267:Injections; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration; D013997:Time Factors
D018377:Neurotransmitter Agents; D008012:Lidocaine; D000661:Amphetamine; D003042:Cocaine