Abstract
The effect of different ligands for the GABA‐BZD receptor and the NMDA receptor were studied in rats trained to discriminate (−)‐nicotine (1.9 μmol/kg) from saline in a standard two‐bar operant conditioning paradigm with food reinforcement. MK‐801 (0.03–0.3 μmol/kg), flumazenil (10–30 μmol/kg), and Ro 15–4513 (3–10 μmol/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 μmol/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 μmol/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 μmol/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. © Wiley‐Liss, Inc.