Effects of cross‐drug preexposure on cocaine‐ and vanoxerine‐induced conditioned taste aversions

Although cocaine readily induces conditioned taste aversions (CTA), little is known about the mechanisms underlying this effect. Since cocaine is a nonselective monoamine transport inhibitor, it has been suggested that its effects at one of the monoamines may mediate this suppression. The present series of studies used the cross‐drug preexposure design to determine if vanoxerine (GBR 12909), a selective dopamine (DA) transporter inhibitor, and cocaine induce aversions by a common mechanism (increases in DA activity). Male Sprague‐Dawley rats were exposed to GBR 12909 (32 mg/kg) prior to aversion conditioning with cocaine (18 mg/kg), GBR 12909 (32 mg/kg) or vehicle. All injections were subcutaneously administered. A 2 × 3 × 4 mixed‐model ANOVA revealed significant effects of Trial, Preexposure drug and Conditioning drug, as well as significant Trial × Preexposure drug and Trial × Conditioning drug interactions. A One‐way ANOVA on the Final Aversion Test revealed significant group differences. Fisher LSD post hoc analysis revealed that preexposure to GBR 12909 attenuated aversions induced by itself, but had no effect on cocaine‐induced aversions. Since cocaine‐induced CTAs were not attenuated by GBR 12909 preexposure (whose major action is inhibition of DA reuptake), it is unlikely that DA plays a significant role in cocaine‐induced CTAs. This work was supported by a Mellon Foundation grant to A.L.R.