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-administr ation is restricted, animals tend to limit intake to a certain level over t ime and across doses. This observation suggests an endogenous constraint or set point that determines the individual's preferred level of pharmacologi cal effects. Objectives. To assess whether the transition to increased leve ls of drug intake is associated with a change in set point. Methods: Two gr oups of rats were trained on a 1-h continuous schedule of cocaine self-admi nistration (250 mu g/injection), after which access to cocaine was increase d 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, diffe rent 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 r educe any temporal limitations on self-injections and subjects were tested several times. Results: In LgA rats, the first hour intake escalated over t ime and eventually reached a level 200% greater than that of ShA rats. Thou gh all rats maintained relatively constant intake across doses, LgA rats to ok nearly two times as much cocaine than ShA rats. When access to cocaine f or LgA rats was reduced to 1 h, intake returned very slowly toward pre-esca lation levels but was still elevated even after 2 months of reduced availab ility. Conclusions: These data suggest that the transition to escalated lev els of intake is associated with a long-lasting change in cocaine set point .