THE NITRIC-OXIDE SYNTHASE INHIBITOR L-NAME (N-OMEGA-NITRO-L-ARGININE METHYL-ESTER) DOES NOT PRODUCE DISCRIMINATIVE STIMULUS EFFECTS SIMILARTO ETHANOL

N-methyl-D-aspartate (NMDA) antagonists substitute for the discriminat ive stimulus effects of ethanol, indicating that a component of ethano l's behavioral activity is produced via blockade of NMDA receptor/chan nel function. Recently, it has been reported that ethanol inhibits NMD A-stimulated nitric oxide synthase (NOS) activity in cortical neurons, thereby decreasing the formation of nitric oxide (NO) in the brain. T hese findings suggest that some of the behavioral effects of ethanol m ay be mediated by inactivation of NOS. The present study examined the role of NO formation in mediating the discriminative stimulus effects of ethanol. To address this hypothesis, an NOS inhibitor, N omega-nitr o-L-arginine methyl ester (L-NAME) and an NMDA competitive antagonist, -4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPPene), wer e administered to two groups of rats trained to discriminate 1.5 g/kg of ethanol (n = 6) or 2.0 g/kg (n = 7) of ethanol from water. After tr aining, dose ranges of CPPene (3 to 17 mg/kg, ip) and L-NAME (100 to 7 80 mg/kg, ip) were tested for ethanol-like effects. L-NAME was also te sted under a range of pretreatment times (20, 60, 90, and 120 min). An additional group of rats trained to discriminate 2.0 g/kg (n = 7) of ethanol from water was also tested with CPPene (10 mg/kg, ip) and L-NA ME (100 and 300 mg/kg, ip) to verify data gathered from the original 2 .0 g/kg of ethanol group tested with L-NAME after a 20-minute pretreat ment Although overall, 17 of 20 animals trained to discriminate ethano l from water exhibited complete substitution of CPPene for ethanol, L- NAME, without affecting response rates, did not consistently substitut e for either 1.5 g/kg or 2.0 g/kg of ethanol. These results indicate t hat inhibition of NO formation is less effective than direct NMDA rece ptor antagonism in producing ethanol-like discriminative stimulus effe cts.