EFFECTS OF MEDIAL PREFRONTAL OR ANTERIOR CINGULATE CORTEX LESIONS ON RESPONDING FOR COCAINE UNDER FIXED-RATIO AND 2ND-ORDER SCHEDULES OF REINFORCEMENT IN RATS

Four experiments examined the effects of excitotoxic. axon-sparing les ions of the medial prefrontal cortex or anterior cingulate cortex in r ats on responding under different schedules of intravenous cocaine sel f-administration and on the locomotor stimulant effects of cocaine. Ex periment 1 tested the acquisition and maintenance of cocaine self-admi nistration under a fixed ratio schedule. Rats with medial prefrontal c ortex lesions showed facilitated acquisition and enhanced responding f or low doses of-the drug when lesions were induced before self-adminis tration behaviour was established. Lesions of the anterior cingulate c ortex did not affect cocaine self-administration. In experiment 2, rat s were trained to respond under a second-order schedule of cocaine rei nforcement, when responding during the fixed interval was reinforced b y presentation of a cocaine-associated visual stimulus under fixed-rat io contingencies. In control rats, these schedule conditions were foun d to maintain high rates of responding and a scalloped pattern of resp onding over time. Omission of conditioned stimulus presentation during the fixed interval significantly disrupted response patterns, confirm ing that the stimulus served to maintain responding during the fixed i nterval. By contrast, rats with medial prefrontal cortex lesions showe d higher rates and disrupted patterns of responding that were unchange d by stimulus omission. Rats with lesions of the anterior cingulate co rtex responded at high rates throughout the fixed interval under all t est conditions, indicating that the cocaine-associated stimulus did no t serve to maintain temporal patterns of responding in these rats. Exp eriment 3 demonstrated the lack of effect of either lesion on the acqu isition of responding for a non-drug reinforcer, sucrose. In experimen t 4, measures of spontaneous and cocaine-induced locomotor activity re vealed that rats in both lesion groups were significantly more active than controls regardless of test conditions. These data indicate that facilitated acquisition of cocaine self-administration and disrupted r esponse patterns under second-order schedule contingencies may result from deficits in behavioural inhibition induced by medial prefrontal c ortical lesions that contrast with deficits following damage to other limbic cortical regions, such as the basolateral amygdala or anterior cingulate cortex.