The objective of this proposal is to provide the first characterizations of the activity of single neurons receiving dopaminergic synaptic input (nucleus accumbens, striatum and medial prefrontal cortex) during intravenous self-administration of cocaine. Units will be categorized with respect to their physiological and behavioral properties in order to establish a background for interpreting neuronal responses to cocaine. Substantial evidence indicates that a critical mechanism by which psychomotor stimulants produce motor output is via facilitation of dopaminergic transmission to accumbens and striatal neurons, and that this effect on accumbens neurons also underlies the reinforcing properties of activity, cocaine dose (cumulative infusions) and motor variables influenced by the drug (e.g., locomotion, stereotypy). To evaluate whether single cells reveal any firing patterns that might uniquely represent responses to cocaine as a reinforcer, comparisons will be made between animals self-administering vs yoked controls (contingent vs noncontingent delivery). Comparisons will be made across days in all the above measures to evaluate whether any changes occur as a function of chronic self- administration of cocaine (2-5 weeks). Neuronal firing patterns will be characterized during administration of other types of reinforcers, such as self-stimulation of the medial forebrain bundle/ventral tegmental area, or food consumption. Patterns of neuronal activity showing similarities or differences across reinforcers or across brain structures could aid in understanding neuronal reward mechanisms involved in drug abuse.
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