Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice

Mice of the C5SBL/6J strain were trained to discriminate between nicotine (1.2 mg/kg) and saline in a two-lever drug discrimination procedure under a tandem variable-interval 60 s fixed-ratio 10 schedule of food reinforcement. Mice of the same strain were trained in conditioned taste aversion (CTA) experiments where drinking a saccharin or saline solution was paired with injection of nicotine or vehicle. During testing with both flavours presented simultaneously, a reduction in the intake of the nicotine-paired solution indicated CTA. The nicotine discrimination was acquired successfully and nicotine yielded a steep dose-response curve. The competitive nicotinic antagonist dihydro-beta -erythroidine (DH betaE, 0.6-3.0 mg/kg) shifted the dose-response for the discriminative stimulus effect of nicotine to the right; the alpha7 nicotinic receptor antagonist methyllycaconitine (MLA, 1.0-10 mg/kg) had no effect. The mice showed strong CTA to 2.0 mg/kg of nicotine and marginally to 0.6 and 1.2 mg/kg of nicotine. DH betaE (3.0-5.6 mg/kg) attenuated the CTA while MLA (1.0-10 mg/kg) had no effect. These studies show that nicotine has discriminative and aversive stimulus properties in C57BL/6J mice and that the effects are mediated primarily by receptors sensitive to DH betaE; there was no evidence for the involvement of alpha7 nicotinic receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.