Rationale: We have previously described a model in which adult outbred male Sprague-Dawley rats are classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on acute cocaine-induced open-field activation. This model revealed important individual differences in cocaine's effects, including that LCRs exhibited greater responding than HCRs on a progressive ratio schedule of cocaine reinforcement. However, no LCR/HCR differences in acquisition of cocaine self-administration (0.25 mg/kg/12 s infusion) were observed under these conditions.

Objectives: To determine if LCRs and HCRs differ in the effectiveness of cocaine to function as a reinforcer under a broader range of conditions, the present study assessed the acquisition of cocaine self-administration (fixed ratio 1 schedule of reinforcement) as a function of i.v. cocaine dose (0.1875, 0.375, 0.5, 1, or 1.5 mg/kg/6 s infusion).

Results: LCRs and HCRs did not differ significantly on any measure of acquisition examined, including the day to meet acquisition criterion, percent acquired, and cocaine intake. The effect of dose on percent acquired and rate of acquisition peaked at the 1-mg/kg/infusion dose of cocaine. In contrast, the effect of dose on cocaine intake was linear, with the highest rate of intake occurring at the 1.5-mg/kg/infusion dose of cocaine.

Conclusions: LCRs and HCRs do not appear to differ in their acquisition of cocaine-reinforced operant responding across a range of cocaine doses, including conditions that lead to high levels of cocaine intake.