Cross-sensitization of the reinforcing effects of cocaine and amphetamine in rats

Abstract

Rationale: Cross-sensitization between cocaine and amphetamine has been demonstrated in different behavioral paradigms. There is a relative paucity of studies examining whether cross-sensitization occurs between amphetamine and cocaine when both are self-administered.

Objective: The current study was designed to test whether animals sensitized to the reinforcing effects of cocaine would show cross-sensitization of the reinforcing effects of amphetamine, using a self-administration paradigm.

Materials and methods: Male, Sprague-Dawley rats were trained to self-administer cocaine and given limited or high exposure to cocaine under a fixed ratio (FR) 1 procedure. After the initial exposure to cocaine, animals self-administered cocaine (1.5 mg/kg per injection) under a progressive ratio (PR) procedure. Subsequently, breakpoints on a PR schedule and rates of intake on an FR schedule maintained by different doses of amphetamine were assessed.

Results: Animals with high initial exposure to cocaine (40 injections of 1.5 mg/kg per injection per day for 5 days) showed stable breakpoints throughout testing. Animals given limited initial cocaine exposure (20 injections of 0.75 mg/kg per injection for 1 day) produced a gradual increase in breakpoints maintained by cocaine over time (i.e., sensitization of the reinforcing effects of cocaine). When subsequently tested with amphetamine, the dose-effect curve was shifted upward in the limited-exposure group relative to the high-exposure group, suggesting cross-sensitization of the reinforcing effects of amphetamine.

Conclusions: Sensitization of the reinforcing effects of cocaine resulted in cross-sensitization of the reinforcing effects of amphetamine. This phenomenon occurs even when both drugs are self-administered.