Long-lasting increase in the set point for cocaine self-administration after escalation in rats

Rationale: When access time to a continuous schedule of drug self-administration is restricted, animals tend to limit intake to a certain level over time and across doses. This observation suggests an endogenous constraint or set point that determines the individual's preferred level of pharmacological effects. Objectives. To assess whether the transition to increased levels of drug intake is associated with a change in set point. Methods: Two groups of rats were trained on a 1-h continuous schedule of cocaine self-administration (250 mu g/injection), after which access to cocaine was increased to 6 h in one group (Long Access or LgA rats) or kept to 1 h in the other group (Short Access or ShA rats). After 22 sessions on this regimen, different doses of cocaine were tested (31.25, 62.5, 125, and 250 mu g/injection). For each dose, the post-response time-out period was reduced to 4 s to reduce any temporal limitations on self-injections and subjects were tested several times. Results: In LgA rats, the first hour intake escalated over time and eventually reached a level 200% greater than that of ShA rats. Though all rats maintained relatively constant intake across doses, LgA rats took nearly two times as much cocaine than ShA rats. When access to cocaine for LgA rats was reduced to 1 h, intake returned very slowly toward pre-escalation levels but was still elevated even after 2 months of reduced availability. Conclusions: These data suggest that the transition to escalated levels of intake is associated with a long-lasting change in cocaine set point.