Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909

Abstract

Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. It has been suggested that its inhibitory effects at one of the monoamine transporters may be mediating this suppression. Using the cross-drug preexposure preparation, the present series of studies examined a possible role of dopamine (DA) in this effect. Male Sprague-Dawley rats were exposed to cocaine (18 mg/kg; Experiment 1) or the selective DA transporter (DAT) inhibitor GBR 12909 (50 mg/kg; Experiment 2) prior to the pairing of a novel saccharin solution with injections of GBR 12909 (32 mg/kg), cocaine (18 mg/kg) or vehicle in a conditioned taste aversion (CTA) procedure. Preexposure to cocaine attenuated aversions induced by itself but not aversions induced by GBR 12909 (Experiment 1). Conversely, preexposure to GBR 12909 attenuated aversions induced by itself and cocaine (Experiment 2). This asymmetry suggests that cocaine and GBR 12909 induce CTAs via similar, but non-identical, mechanisms. These data are discussed in the context of previous work demonstrating roles for dopamine, norepinephrine and serotonin in cocaine-induced CTAs.

Fig. 1

Mean (± SEM) saccharin consumption (ml) for all subjects in groups preexposed to cocaine or vehicle and conditioned with cocaine (18 mg/kg), GBR 12909 (32 mg/kg) or vehicle. All cocaine-preexposed subjects (regardless of conditioning drug) drank significantly more than vehicle-preexposed subjects (regardless of conditioning drug) on Trials 2 and 3. All drug-conditioned subjects (collapsed across preexposure condition) drank significantly less than all vehicle-conditioned subjects (collapsed across preexposure condition) on Trials 2, 3 and 4. Since no significant three-way interaction was observed, no post-hoc analyses were run on individual groups.

Fig. 2

Mean (±SEM) saccharin consumption (ml) for all subjects in groups preexposed to GBR 12909 (50 mg/kg) or vehicle and conditioned with cocaine (18 mg/kg), GBR 12909 (32 mg/kg) or vehicle. *Significantly different from Group VEH–VEH; ^#Significantly different from Group GBR–GBR; ^Significantly different from Group GBR–COC.