The ascending limb of the cocaine dose-response curve for reinforcing effect in rhesus monkeys

Rationale: To date, the literature on the intravenous self-administration of cocaine by laboratory animals lacks a compelling demonstration of an ascending limb to the dose-response function. It has been argued that previous demonstrations of an ascending limb are confounded by the extinction process. Objective: The objective was to examine the relationship between cocaine dose and intravenous self-injection frequency at the low end of the cocaine dose range (0.03-0.00075 mg/kg per injection). Methods: Three adult rhesus monkeys were given the opportunity to self-inject cocaine on a fixed-ratio 1 schedule of reinforcement with no timeouts between injections. Single cocaine doses were presented for between 13 and 27 consecutive 2-h sessions in the order of 0.03, 0.01, 0.003, 0.0015_a, 0.00075, and 0.0015_b mg/kg per injection. Results: An ascending limb of the cocaine dose-response curve was found to exist between the doses of 0.00075 and 0.003 mg/kg per injection. Conclusions: The fact that response rate increased from 0.00075 to 0.0015_b mg/kg per injection, and remained stable at this intermediate level, negates the possibility that responding at 0.0015_b mg/kg per injection is an artifact of experimental extinction. The finding that significantly less cocaine was taken at 0.0015_b mg/kg per injection than at higher doses demonstrates that satiety was not the mechanism by which cocaine intake was regulated on the ascending limb of the dose-response curve.