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

Mice of the C56BL/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-β-erythroidine (DHβE, 0.6–3.0 mg/kg) shifted the dose–response for the discriminative stimulus effect of nicotine to the right; the 7 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. DHβE (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 DHβE; there was no evidence for the involvement of 7 nicotinic receptors.