Cocaine-induced conditioned taste aversions: Investigations of neurochemical mediation

Drugs of abuse have both rewarding and aversive effects, and it is the balance of these effects which impact abuse vulnerability. Although research has traditionally focused on the rewarding effects of drugs, their aversive effects have recently gained increasing attention. The present series of investigations sought to determine the neurochemical mediation underlying conditioned taste aversions (CTA) induced by cocaine. Given the role of dopamine (DA) in cocaine reward, this neurotransmitter system is of particular interest. The present experiments used direct pharmacological antagonism (with the DA antagonist haloperidol) as well as cross-drug preexposure (with DA transporter [DAT] inhibitor GBR 12909) to determine a role, if any, of DA in the induction of CTAs by cocaine. Following the determination of behaviorally active doses of haloperidol with no aversive effects on their own (Experiment 1), animals were given 1 mg/kg haloperidol prior to various doses of cocaine in a taste aversion procedure (Experiment 2). Under these conditions, haloperidol blocked cocaine-induced CTAs (at 18 and 32 mg/kg). In separate experiments, cocaine (18 mg/kg; Experiment 3) or GBR 12909 (32 mg/kg; Experiment 4 or 50 mg/kg; Experiment 5) was administered prior to aversion conditioning with cocaine (18 mg/kg) and GBR 12909 (32 mg/kg). Under these conditions, GBR 12909 (at 50 mg/kg only) blocked cocaine-induced CTAs but the reverse serial presentation did not result in significant cross-drug attenuation, indicating that the aversive properties of GBR 12909 and cocaine are similar, but not identical. Although these results indicate a role of DA in cocaine-induced CTAs, the extent to which each DA receptor subtype plays a role remains unknown. These results are discussed in the context of previous work demonstrating roles for both norepinephrine (NE) and possibly serotonin (5-HT) in cocaine-induced CTAs. The neurochemical mediation of cocaine's aversive effects was discussed in the context of the neurochemical mediation of cocaine reward and the implications for drug abuse.