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

Abstract

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.