Dopaminergic mediation of the stimulant generalization of nicotine

1. Experiments were conducted to investigate if the psychostimulant cathinone, like d-amphetamine, would produce generalization of the discriminative stimulus effects of nicotine. 2. Rats were trained to discriminate either 0.8 mg/kg cathinone from its vehicle or 0.8 mg/kg nicotine from its vehicle and, subsequently, administered various doses of the other compound. 3. Results of Exp 1 indicate that animals trained to discriminate cathinone only partially generalize to the effects of 0.8-1.6 mg/kg nicotine. In contrast, animals trained to discriminate nicotine dose-responsively generalize to cathinone doses ranging from 0.1-1.2 mg/kg. 4. Exp 2 served to investigate the effects of the dopamine release inhibiting drug CGS 10746B upon the observed cathinone generalization in nicotine-trained rats. Pretreatment with this compound at doses of 20 and 30 mg/kg significantly attenuated cathinone generalization in these animals. 5. The results are discussed in light of the growing evidence that nicotinic receptors reside upon mesolimbic dopamine neurons and the possibility that the consequent increase in extracellular dopamine may produce the discriminative stimuli, as well as the reinforcing properties, of nicotine.