Decreased reinforcing effects of cocaine following 2 weeks of continuous d-amphetamine treatment in rats

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Abstract
Rationale Recent studies have investigated d-amphetamine as a potential agonist medication for cocaine dependence. In rats, a 14-day continuous infusion of d-amphetamine via osmotic mini-pump has been shown to decrease cocaine-reinforced responding under a progressive ratio (PR) schedule of reinforcement. Objectives This study was designed to assess the influences of the d-amphetamine treatment dose and self-administered cocaine dose on the magnitude of this effect. Materials and methods Experiment 1: rats were trained to self-administer 1.5 mg/kg/inj cocaine under a PR schedule, then implanted with d-amphetamine mini-pumps for 14 days (days 1–7, 5 mg/kg/day; days 8–14, 7.5 mg/kg/day). Breakpoints were evaluated throughout the treatment period and 14 days post-treatment. Experiment 2: rats were trained to self-administer cocaine under a PR schedule and initial dose–response curves were determined before implantation of d-amphetamine mini-pumps. During the 14-day d-amphetamine (5 mg/kg/day) treatment period, rats self-administered one of four cocaine doses (0.19, 0.38, 0.75, or 1.5 mg/kg/inj). A post-treatment PR dose–response curve and responding under a fixed ratio 1 (FR1) schedule were evaluated after mini-pump removal. Results Experiment 1: breakpoints for 1.5 mg/kg/inj cocaine were unchanged by the increasing dose of d-amphetamine. Experiment 2: the PR dose–response curve was shifted downward after the treatment period in rats that had self-administered 0.19 and 0.38 mg/kg/inj cocaine. In contrast, rats in the 0.75 and 1.5 mg/kg/inj groups demonstrated increased rates of cocaine intake under an FR1 schedule after the treatment period. Conclusions These data suggest that continuous d-amphetamine treatment attenuates the reinforcing effects of cocaine.

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