Possible role of norepinephrine in cocaine-induced conditioned taste aversions

Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. The present series of studies used the cross-drug preexposure design to determine if desipramine (DMI), a selective NE transporter (NET) inhibitor, and cocaine (a nonselective monoamine transport inhibitor) induce aversions by a common mechanism, specifically increases in NE activity. Male Sprague-Dawley rats were exposed to DMI prior to aversion conditioning with cocaine (Experiment 1) and with cocaine prior to aversion conditioning with DMI (Experiment 2). All drugs were administered subcutaneously at 18 mg/kg. Preexposure to DMI attenuated aversions induced by cocaine. However, preexposure to cocaine did not weaken DMI-induced aversions and, in fact, potentiated aversions induced by DMI on several trials. The asymmetrical results are discussed in terms of the possible role NE might play in the mediation of aversions induced by cocaine. Additionally, serial use of these compounds is discussed in terms of clinical implications.