Cocaine extended access gates compulsive-like seeking in rats

When does compulsive-like drug seeking emerge? Despite decades of research, and critical advances in our understanding of brain processes leading to addiction, this question remains widely unanswered. So far, behavioral models assessing compulsive-like cocaine seeking following an extended access to cocaine failed to capture the development of its compulsive seeking. In fact, compulsive-like animals immediately displayed pathological seeking when facing its negative consequences of drug seeking, usually materialized by an unescapable mild electric shock on the paws. Here, we designed a new task, ‘Punished Seeking during Extended access’ (PSE), by inserting punished seeking trials within the sessions of extended access to cocaine. We show that compulsive-like cocaine seeking progressively emerges after several PSE sessions, once cocaine intake has been escalated. We thus provide the addiction community a pertinent model to explore brain mechanisms sustaining the emergence of compulsive-like cocaine seeking.