Discrimination of ethanol in rats: effects of nicotine, diazepam, CGP 40116, and 1-(m-chlorophenyl)-biguanide.

The drug discrimination paradigm was used to evaluate the role of certain ligand-gated ion channels in the discriminative stimulus properties of ethanol. Rats were trained to discriminate ethanol (1.0 g/kg) from saline vehicle under the FR10 schedule of sweetened milk reinforcement. The discrimination of lower ethanol doses was enhanced by either the GABA(A) receptor positive modulator, diazepam (0.5 mg/kg), or nicotinic acetylcholine receptor agonist, nicotine (0.3 mg/kg). Neither diazepam nor nicotine produced any effect on the rate of responding. Both the NMDA receptor competitive antagonist, CGP 40116 (0.5 mg/kg) and the 5-HT) receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg) enhanced the cueing properties of lower ethanol doses, but these effects were associated with a significant reduction in the response rate. The ethanol-like stimulus effects produced by diazepam or CGP 40116 were not influenced by 0.3 mg/kg nicotine. In contrast, CGP 40116 moderately enhanced the ethanol-like stimulus effects of diazepam. The present results show that: 1) pretreatment with nicotine, diazepam, CGP 40116 or 1-(m-chlorophenyl)-biguanide enhance the ethanol discrimination; 2) neither the GABA(A) nor the NMDA receptor complex alone is critically involved in the nicotine-induced enhancement of the ethanol discrimination; 3) NMDA receptor competitive antagonist and GABAergic benzodiazepine derivative may produce moderate additive effects in rats trained to discriminate ethanol.