Extended Access to Cocaine Self-Administration Enhances Drug-Primed Reinstatement but Not Behavioral Sensitization

Abstract

Cocaine addicts increase the frequency and amount of drug use over time. This characteristic has been modeled by escalating drug intake in rats that were given extended access to cocaine. However, it remains unclear whether the behavior of escalating drug intake or simply increased drug dose is the relevant aspect of this model. The present study investigated whether the phenomenon of escalated drug-taking enhances cocaine-induced sensitization and reinstatement. Rats were trained to self-administer cocaine during daily 1-h sessions for 7 days. A short-access (ShA) group continued to receive 1-h sessions for 10 days while a group of rats was switched to 6 h of drug access, long-access (ShA-LgA) group, for 10 days. In addition, a long-access only (LgA-only) group was added that was not pretrained but was only given extended access for 10 days. ShA subjects maintained stable drug intake; ShA-LgA subjects escalated intake while LgA-only subjects decreased drug intake. All groups displayed an inverted-U shaped cocaine dose-response curve in both the sensitization and reinstatement tests. There was no difference in the expression of behavioral sensitization between groups. Whereas both long-access groups showed reinstatement at more doses of cocaine than the ShA group, the presence of escalation did not affect reinstatement. These results indicate that extended access to cocaine self-administration produces behavioral differences relative to traditional short-access animals in reinstatement, but not sensitization. Furthermore, the differences in reinstatement are predicted more by length of cocaine access than by escalation of drug intake.