The Effects of Extended-Access Cocaine Self-Administration on Working Memory Performance, Reversal Learning and Incubation of Cocaine-Seeking in Adult Male Rats.

Cocaine use disorder is characterized not only by the high rate of relapse, but also by deficits in cognition and prefrontal cortical function. Still, the relationship between cognitive impairment and cocaine-seeking remains poorly understood. The current study used a rodent model to determine the effects of extended access cocaine self-administration on cognitive performance in a prefrontal cortex-dependent delayed match-to-sample/non-match-to-sample (DMS/DNMS) task. Further, this study sought to investigate how post-cocaine changes in cognitive performance correlate with cue/context-induced cocaine-seeking following a prolonged period of abstinence. Animals were trained to self-administer cocaine during 6 daily 1 hour-long sessions followed by 12 days of extended, 6 hour-long access. The extended access cocaine rats exhibited robust self-administration behavior and escalation of cocaine intake. Next, DMS/DNMS task was used to evaluate working memory capacity and reversal learning performance over a range of 0 - 30 s delays. Although this study failed to detect a major cognitive impairment, extended access to cocaine resulted in the persistent working memory/DMS deficit at a moderate cognitive load (10 s delay). There were no changes in the reversal learning/DNMS performance. It is likely that the parameters of the DMS/DNMS task, as used in the current study, exceeded acquisition capacity of rats thus obscuring cocaine effects at longer delays. Finally, rats showed a robust relapse of context/cue-elicited cocaine-seeking following the 45 - day abstinence. However, the intensity of cocaine-seeking did not correlate with the deficit in the DMS task. In conclusion, future studies must re-evaluate whether a more robust relationship between post-cocaine cognitive performance and cocaine-seeking can be detected under adjusted DMS/DNMS conditions.