Discriminative stimulus properties of ethanol in rats: studies on the role of nitric oxide

The present study examined the role of the L-arginine-nitric oxide pathway in mediation of the ethanol interoceptive (discriminative) cue. Adult male Wistar rats (n = 16) were trained to discriminate ethanol (1 g/kg, 10% v/v) from saline under a fixed-ratio 10 (FR10) schedule of sweetened milk reinforcement. A nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 10-540 mg/kg) did not substitute for ethanol. Similarly, a relatively selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 10-80 mg/kg), did not mimic the ethanol cue. However, both L-NAME and 7-NI produced significant reduction in the rate of operant responding. A nitric oxide precursor, L-arginine (100-500 mg/kg) neither substituted for nor antagonize the ethanol stimulus. Taken together, these results suggest that the L-arginine-nitric oxide pathway is not involved in mediation of the discriminative stimulus effects of ethanol in the rat.