The behavioural and prefrontal cortical mechanisms for extinction and recovery of alcoholic beer-seeking

The present thesis investigated the behavioural and prefrontal cortical mechanisms underlying extinction and recovery of drug-seeking. Rats were trained to self-administer alcoholic beer, extinguished, and then recovery of drug-seeking was assessed using one of two preparations. In reacquisition, the rate of retraining to self-administer alcoholic beer was examined after extinction training. In renewal, animals were tested without reinforcement in the self-administration context, where drug-seeking recovered, and the extinction context, where there were low levels of drug-seeking. The first series of experiments examined the role of context in the reacquisition of extinguished alcoholic beer-seeking. These experiments showed that reacquisition was rapid compared to a naive control and not simply a function of the amount of extinction training. Importantly, reacquisition was independent of context. That is, retraining was rapid regardless of whether testing occurred in a novel context (AAB), a context with a mixed history of reinforcement (AAA), the extinction context (ABB) or the self-administration context (ABA). In contrast, latencies to first drug-associated response were delayed when animals were tested in a context uniquely associated with extinction training. Together, these findings suggest that two different behavioural processes influence latencies and overall reacquisition. Specifically, latencies were dependent on the physical context whereas overall responding during reacquisition was dependent on the contingency context. The second series of experiments examined medial prefrontal cortical (mPFC) control of extinction, renewal and reacquisition of drug-seeking. These experiments tested the proposed reinstatement extinction dichotomy within the prelimbic (PL) and infralimbic (IL) mPFC regions. Reversible inactivation of PL prior to test attenuated ABA renewal but augmented reacquisition. IL reversible inactivation prior to test had no effect on ABA renewal or extinction expression (AAA and ABB). IL inactivation did, however, delay latency to first response when testing occurred in the extinction context. Manipulation of the DP had no effect on any measures suggesting that it is a functionally distinct region from the neighbouring IL. Together, these results do not support a reinstatement extinction dichotomy within PL and IL. Rather, they suggest that PL mediates retrieval of contingency information. In contrast, IL may be recruited to regulate responding after extended training