Neural mechanisms involved in the development of addiction-like symptoms

National Institute On Drug Abuse

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Abstract

Cocaine seeking progressively increases during abstinence, a phenomenon termed incubation of cocaine craving. Incubation of cocaine craving has been demonstrated after limited (2-h daily sessions) or extended access (6-h daily sessions) continuous cocaine self-administration. Recently, Zimmer et al. (NPP 2012) introduced an intermittent access self-administration procedure in which rats have access to cocaine for 5 min every 25 min during the daily sessions. They showed that this procedure increases the motivation to self-administer cocaine. Here, we studied whether intermittent cocaine self-administration would increase incubation of cocaine craving in male and female rats. We first trained male and female rats to self-administer cocaine (0.75 mg/kg/infusion) continuously or intermittently for 12 days for 8-h/day. We found, in both male and female rats, an escalation of cocaine self-administration over 12-day drug sessions under both training conditions. Then, we assessed drug seeking in relapse tests after 2 or 29 abstinence days. During testing, lever presses were not reinforced with cocaine (extinction conditions). Both male and female rats lever pressed significantly more after 29 abstinence days than after 2 days (incubation of cocaine craving) under both training conditions. More importantly, in both male and female, we found a significant increase in drug seeking on both day 2 and 29 after intermittent cocaine access compared to continuous access. Moreover, prior intermittent cocaine access significantly potentiated incubation of cocaine craving (a significant interaction of access condition x abstinence day) in female but not male rats. Our results demonstrate that females are more susceptible to the potentiation effect of prior intermittent cocaine access on relapse after prolonged abstinence.