MODULATION OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF (-)-NICOTINE BY DIAZEPAM AND ETHANOL

The effect of different ligands for the GABA-BZD receptor and the NMDA receptor were studied in rats trained to discriminate (-)-nicotine (1.9 mu mol/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. MK-801 (0.03-0.3 mu mol/kg), flumazenil (10-30 mu mol/kg), and Po 15-4513 (3-10 mu mol/kg) did not generalize to (-)-nicotine on nicotine-trained rats, and when tested as antagonists they did not block the nicotine cue. Diazepam (3-10 mu mol/kg) and ethanol (11-22 mmol/kg) did not have any effect by themselves, but they significantly attenuated the nicotine cue by 53 and 65%, respectively, without affecting the response rates of the animals. Pre-treatment with flumazenil (30 mu mol/kg) reversed the effect of diazepam but it did not reverse the effect of ethanol on the discriminative stimulus properties of (-)-nicotine. The effect of ethanol was not blocked by Ro 15-4513 (10 mu mol/kg). These data indicate that diazepam and ethanol modulate the expression of the nicotine cue and that the effect of diazepam is mediated via a benzodiazepine receptor mechanism. (C) 1995 Wiley-Liss, Inc.