Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats

Abstract

Escalated, binge-like patterns of cocaine self-administration are engendered by repeated, intermittent exposure to episodes of social defeat stress, as well as by extended drug access. The present study investigated if prior exposure to brief episodes of social defeat stress would intensify the escalation of cocaine self-administration associated with extended access conditions. The consequences of both stress sensitization and prolonged access were further assessed with progressive ratio (PR) break points and during a 24-h variable dose "binge". Male Long-Evans rats were exposed to four episodes of defeat stress (days 1-4-7-10), and their locomotor response to cocaine was assessed 10 days later. Rats were subsequently implanted with intravenous catheters. After acquisition, stressed and control rats were allowed daily short (1 h/day) or extended (6 h/day) sessions of cocaine self-administration for 14 days (0.75 mg/kg/infusion). In sequence, we determined break points for cocaine on PR tests and assessed drug intake patterns during a 24-h variable dose binge. Defeat stress induced cross-sensitization to a cocaine challenge, increased break points for cocaine, and produced persistent, escalated cocaine taking during a 24-h binge. Rats with extended access to cocaine-both stressed and controls-similarly escalated their drug intake throughout the 14 days. Extended access conditions accelerated the rate of cocaine self-administration in the first half of the binge, indicated by shorter post-infusion intervals, but failed to amplify the accumulated drug intake in non-stressed controls. Both social defeat stress and drug access conditions may engender escalated cocaine intake via distinct mechanisms that regulate drug self-administration.