Impaired decision making following escalation of cocaine self‐administration predicts vulnerability to relapse in rats

摘要

Abstract Impairments in cost‐benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague‐Dawley rats were trained to self‐administer (SA) cocaine during 19 daily long‐access (12‐h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli–, stress‐, and drug‐primed reinstatement challenges. The influence of escalated cocaine intake on decision making was measured over time by four test sessions of a rodent analogue of the Iowa Gambling Task (rGT), once prior to cocaine exposure and then 1?day, 1?week, and 1?month after the last SA session. Substantial individual variability was observed in the influence of escalated cocaine SA on decision‐making performance. A subset of rats displayed pronounced deficits, while others showed unaffected or even improved performance on the rat Gambling Task (rGT) 24?hours after the last SA session. When challenged with a relapse test after 1?week of forced abstinence, animals that showed impaired decision making following SA displayed an increased propensity to respond for cocaine under extinction. These data suggest that decision‐making deficits in individuals with drug addiction are not antecedent to—but arise as a consequence of—drug exposure. Moreover, these data indicate that susceptibility to the deleterious effects of drugs on decision making confers vulnerability toward relapse.