Neural mechanisms involved in the development of addiction-like symptoms

National Institute On Drug Abuse

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Abstract

BACKGROUND: Studies using continuous access self-administration procedures showed that cocaine seeking progressively increases during abstinence (incubation of cocaine craving). Recently, studies using intermittent access self-administration procedures showed increased motivation to self-administer and seek cocaine. Here, we examined whether intermittent access cocaine self-administration would potentiate incubation of cocaine craving in male and female rats, and the role of estrous cycles in incubation. METHODS: In Experiment 1, male (n=52) and female (n=47) rats self-administered cocaine either continuously (8-h/d) or intermittently (5-min ON, 25-min OFF x 16) for 12 days, followed by relapse tests after 2 or 29 abstinence days. In Experiment 2-3, female rats self-administered cocaine intermittently for 6 (n=16), 12 (n=32), or 18 (n=16) sessions, followed by relapse tests after 2 or 29 abstinence days. In Experiment 3, the estrus cycle was measured using a vaginal smear test. RESULTS: Incubation of cocaine craving was observed in both sexes after either intermittent or continuous access drug self-administration. Independent of access condition and abstinence day, cocaine seeking was higher in females than in males. In both sexes, cocaine seeking on both abstinence days was higher after intermittent drug access than after continuous drug access. In females, incubation of craving after intermittent drug access occurred during the estrous phase, but not the non-estrous phases; this effect was independent of the training duration. CONCLUSION: In both sexes, intermittent cocaine access caused time-independent increases in drug seeking during abstinence. In females, the time-dependent increase in drug seeking (incubation) is dependent on the estrus cycle phase.