The effects of cross‐drug preexposure on cocaine‐ and fluoxetine‐induced conditioned taste aversions

Abstract

Although cocaine‐induced CTAs are well documented, little is known about the basis for cocaine's aversive effects. To address a role of serotonin (5‐HT) in cocaine‐induced aversions, the present experiments used the cross‐drug preexposure design in which the effects of preexposure to fluoxetine (FLU), a selective 5‐HT transporter (SERT) inhibitor, were examined on aversions induced by cocaine (nonselective monoamine transport inhibitor) and the effects of cocaine preexposure were examined on FLU‐induced aversions. A FLU dose‐response function was established in male Sprague‐Dawley rats to determine a dose of FLU that would induce intermediate aversions comparable to those induced by 18 mg/kg cocaine (Experiment 1). Naïve rats were then exposed to FLU (10 mg/kg) prior to aversion conditioning with cocaine (18 mg/kg ; Experiment 2) and with cocaine (18 mg/kg) prior to aversion conditioning with FLU (10 mg/kg; Experiment 3). Although there was no effect of FLU preexposure on either cocaine‐ or FLU‐induced aversions, preexposure to cocaine attenuated aversions induced by itself and by FLU. One interpretation of this attenuation is that exposure to one drug produces cross‐tolerance to the aversion‐inducing effects of the second. These results suggest that these two compounds may induce aversions via a common mechanism, i.e., SERT inhibition. Supported by a Mellon Foundation grant to ALR.