THE EFFECTS OF BEHAVIORAL HISTORY ON COCAINE SELF-ADMINISTRATION BY RHESUS-MONKEYS

The purpose of the present study was to examine whether a history of r esponding under schedules that generate either high or low response ra tes could modify previously established cocaine self-administration. E ight experimentally naive rhesus monkeys were trained to respond on on e of two levers under a fixed-interval (FI) 5-min schedule of intraven ous cocaine (0.03 mg/kg per injection) presentation. When responding w as stable a cocaine dose-response curve (saline, 0.01-0.3 mg/kg per in jection) was determined. Following completion of the dose-response cur ves, the monkeys were randomly assigned to one of two groups (n = 4/gr oup) and trained to respond on the other lever under either a fixed-ra tio (FR) 50 or inter-response times (IRT) > 30-s schedule of cocaine ( 0.03 mg/kg per injection) presentation. After 65 sessions responding w as again maintained under the FI5-min schedule of 0.03 mg/kg per injec tion cocaine for 60 sessions, followed by redetermination of the cocai ne dose-response curve. During the initial exposure to the FI schedule , the mean rate of responding was 4.02 (+/- 0.33) responses/min and th e cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. T he FR50 schedule generated high rates (66.80 +/- 5.6 responses/min), w hile response rates under the IRT > 30-s schedule were low (2.62 +/- 0 .2 responses/min). Following different behavioral histories, response rates under the FIS-min schedule were significantly higher for 60 sess ions in FR-history monkeys compared to IRT-history subjects. Compared to the initial FI baselines, cocaine intake (mg/kg per session) was si gnificantly higher following an FR-history and significantly lower fol lowing 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 fa rther to the right in FR-history subjects compared to IRT-history monk eys. Results from the present study indicate that previously establish ed ''drug-seeking'' behavior can be modified by training under differe nt reinforcement schedules. Knowledge of such historical variables may be important in understanding the determinants of drug self-administr ation.