The effects of behavioral history on cocaine self-administration by rhesus monkeys

Abstract

The purpose of the present study was to examine whether a history of responding under schedules that generate either high or low response rates could modify previously established cocaine self-administration. Eight experimentally naive rhesus monkeys were trained to respond on one of two levers under a fixed-interval (FI) 5-min schedule of intravenous cocaine (0.03 mg/kg per injection) presentation. When responding was stable a cocaine dose-response curve (saline, 0.01–0.3 mg/kg per injection) was determined. Following completion of the dose-response curves, the monkeys were randomly assigned to one of two groups (n=4/group) and trained to respond on the other lever under either a fixed-ratio (FR) 50 or inter-response times (IRT) > 30-s schedule of cocaine (0.03 mg/kg per injection) presentation. After 65 sessions responding was again maintained under the FI5-min schedule of 0.03 mg/kg per injection cocaine for 60 sessions, followed by redetermination of the cocaine dose-response curve. During the initial exposure to the FI schedule, the mean rate of responding was 4.02 (± 0.33) responses/min and the cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. The FR50 schedule generated high rates (66.80 ± 5.6 responses/min), while response rates under the IRT > 30-s schedule were low (2.62 ± 0.2 responses/min). Following different behavioral histories, response rates under the FI5-min schedule were significantly higher for 60 sessions in FR-history monkeys compared to IRT-history subjects. Compared to the initial FI baselines, cocaine intake (mg/kg per session) was significantly higher following an FR-history and significantly lower following training under an IRT schedule, for 60 consecutive sessions. In addition, there was a significant effect of behavioral history on the cocaine dose-response curve, such that descending limb was shifted farther to the right in FR-history subjects compared to IRT-history monkeys. Results from the present study indicate that previously established “drug-seeking” behavior can be modified by training under different reinforcement schedules. Knowledge of such historical variables may be important in understanding the determinants of drug self-administration.