Escalation of cocaine intake with extended access in rats: dysregulated addiction or regulated acquisition?

Abstract

Understanding the neurobehavioral mechanisms underlying dysregulated cocaine intake is important for the development of new cocaine abuse therapies. The current study determined if cocaine escalation under extended access conditions (6-h access) is regulated by discrimination learning processes. Rats were initially trained on cocaine self-administration (0.1 or 0.25 mg/kg/infusion) using a fixed ratio 1 (FR 1) schedule under 1-h access for 12 sessions. Some rats were then trained to self-administer cocaine under 1-h or 6-h access conditions exclusively for 14 additional sessions, while other rats were trained under both 1- and 6-h access conditions that were cued or noncued for 28 additional sessions (14 sessions for each 1- and 6-h access). Two additional groups of rats were initially trained to self-administer cocaine using an FR 1 schedule under 10-min access for 12 sessions; half of the animals were then switched to 60-min access conditions for 14 additional sessions. When access conditions were differentially cued, escalation of cocaine intake was evident in animals with both 1- and 6-h access conditions during the escalation phase. Escalation also was evident in animals initially trained with 10-min access and then switched to 60-min access. The results demonstrate that dysregulated and regulated intakes can be expressed within the same animal, indicating that escalation is context-dependent. Furthermore, escalated cocaine intake can be expressed under 1-h access conditions. Overall, these results suggest that escalated cocaine intake may be representative of discrimination-dependent regulated intake rather than addiction-like, compulsive intake.