Behavioral interaction between cocaine and caffeine: A drug discrimination analysis in rats

Abstract

The effects of caffeine upon the discriminative and rate-altering effects of cocaine were examined in rats. Using a food-reinforced two-lever operant procedure, 12 Sprague-Dawley male rats were trained to discriminate between 10 mg/kg cocaine and saline. Stimulus generalization tests with both cocaine and amphetamine resulted in a dose-related increase in cocaine-appropriate responding. A variable response rate topography was produced by cocaine. Caffeine also engendered a dose-related increase in cocaine-appropriate responding and resulted in a potency ratio of 15:1 when compared to cocaine. In contrast, increasing doses of caffeine produced a biphasic response rate function (first increases and then decreases). Response choice data suggested a potency relationship of amphetamine > cocaine > caffeine. Caffeine potentiated the discriminative stimulus properties of cocaine. Isobolographic analysis characterized this interaction as simple additivity. However, caffeine's effects upon the rate-altering effects of cocaine resulted in a biphasic interaction pattern. With low doses of cocaine in combination with various doses of caffeine, the interaction for rate reduction is best categorized as “supra-additive,” in contrast, increasing either the cocaine dose or caffeine dose could change the interaction to simple additivity and/or infra-additivity.