Reinforcing and aversive effects of caffeine measured by flavor preference conditioning in caffeine-naive and caffeine-acclimated rats

Literature on the stimulus properties of caffeine in rats and humans has described both reinforcing and aversive effects. But some disagreement exists regarding whether caffeine is an effective positive reinforcer for caffeine-naive individuals, and how its stimulus properties change with habitual consumption. These experiments measured the reinforcing/aversive effects of caffeine for rats across a range of concentrations, assayed by conditioned aversion or preference for caffeine-paired flavors, and investigated changes in preference/aversion after extensive prior consumption. In the first two experiments, caffeine-naive rats were trained in sessions alternating daily between a distinctly flavored palatable solution (CS+) containing caffeine (0.07–0.25 mg/ml, yielding actual doses of ∼ 4–31 mg/kg bodyweight) and a differently flavored palatable solution (CS−) without caffeine. In post-conditioning two-bottle choice tests between the CS+ and CS− flavors a clear preference/aversion function was apparent across the range of doses. In a third experiment, extensive acclimation to daily caffeine consumption prior to flavor–caffeine pairing significantly altered the preference/aversion function, apparently by reducing the aversiveness of higher doses, not increasing reinforcement by a low dose. These experiments provide additional evidence for an inherent reinforcing effect for naive rats, and also an effect of prior caffeine consumption history.