Lesions of the dorsomedial frontal cortex block sensitization to the positive-reinforcing effects of cocaine

Abstract

Previous studies have reported that rats exposed to a binge-abstinence history of cocaine self-administration exhibit sensitization to the positive-reinforcing effects of cocaine on a progressive ratio (PR) schedule of reinforcement. The purpose of the present study was to determine whether lesions of the dorsomedial frontal cortex block sensitization to the reinforcing effects of cocaine in rats with a history of binge-abstinence self-administration. Separate groups of male rats received bilateral infusions of either ibotenic acid (lesion) or sterile saline (sham) into the dorsomedial frontal cortex, or were left undisturbed (intact). All rats were then implanted with jugular catheters and trained to self-administer cocaine. Following acquisition, cocaine was made available on a PR schedule of reinforcement and breakpoints were determined in each group. Rats were then exposed to a discrete-trials (DT) procedure in which cocaine was made available during 10-min discrete-trials that occurred every 15 min (i.e., 4 times per hr) during daily, 24-hr sessions. This procedure elicited a "binge" in all groups, during which high rates of responding were maintained over a period of 1-2 days. After 10 days, the DT procedure was terminated, and no cocaine was available for the next 7 days. Following 7 days of forced "abstinence", cocaine-reinforced breakpoints were redetermined on the PR schedule. Prior to the DT procedure, no differences were observed in breakpoints across the three groups. Following the 7-day abstinence period, breakpoints on the PR schedule increased significantly in intact and sham rats, indicating an increase in the reinforcing efficacy of cocaine. In contrast, breakpoints did not increase in lesion rats, and were similar to those obtained prior to the binge-abstinence history. These data suggest that lesions of the dorsomedial frontal cortex block sensitization to the positive-reinforcing effects of cocaine in rats with a history of binge-abstinence self-administration.