Neuronal nitric oxide synthase is resistant to ethanol

To test for a possible role of nitric oxide (NO) in the neurotoxicity of et hanol, we studied the effects of ethanol on the neuronal NO synthase (nNOS) both in vitro and in vivo. Ethanol, up to 200 mM, did not change the NOS a ctivity in the cerebellar homogenate or the production of NO by the culture d cerebellar granule cells. The number of NADPH diaphorase-positive cells i n the culture did not change after the exposure to 200 mM ethanol in vitro. The NOS activity in the various brain regions of mice remained similar to the controls after the acute (3g/kg) and the chronic (33g/kg/day, 3.5 days) administration of ethanol. N(omega)nitro-L-arginine, a NOS inhibitor, did not affect the ethanol withdrawal behavior. These results indicate that nNO S is resistant to ethanol at clinically relevant concentrations and that et hanol affects the NO-operated system in the brain through a pathway other t han that of nNOS.