Role of the prelimbic cortex in the acquisition, re-acquisition or persistence of responding for a drug-paired conditioned reinforcer

The medial prefrontal cortex has been suggested to play a role in drug addiction due to its involvement in the reinstatement of drug seeking. In the present study, the role of the prelimbic cortex in persistent responding maintained by the earned presentations of a drug-paired conditioned reinforcer was studied. Temporary inactivation of the prelimbic, prefrontal cortex of rats had no effect on this persistent response, but did impair its initial acquisition, maintained by the drug-paired conditioned reinforcer. The lesion also impaired re-acquisition of this response after extinction by omission of the contingent conditioned reinforcer. These results suggest that the prelimbic cortex has a selective role in the acquisition, or re-acquisition, of instrumental responses for drug-paired conditioned reinforcers, that may be important in relapse to drug seeking. Anatomical controls with placements in the infralimbic cortex showed longer-lasting impairments in the acquisition of this response, consistent with the suggestion that the prelimbic and infralimbic cortices mediate different aspects of behavior, with the infralimbic being more specialized for habits. The implications of the present findings toward the understanding of drug seeking and relapse behaviors and the separate brain systems that may underlie them are discussed.