BINGE ETHANOL-INDUCED BRAIN-DAMAGE IN RATS - EFFECT OF INHIBITORS OF NITRIC-OXIDE SYNTHASE

Testing the possible role of endogenous nitric oxide (NO) in the neuro toxicity of ethanol, we examined how two different NO synthase (NOS) i nhibitors affected the extent of cerebrocortical and olfactory neurona l damage in a modified ''binge intoxication'' rat model (Collins et al ., Alcohol Clin. Exp. Res. 20:284-292, 1996), Male rats intragastrical ly fed ethanol (6.5 to 12 g/kg/day) in nutrient solution three times d aily for 4 days also received N-G-nitro-L-arginine methyl ester by chr onic intracerebroventricular infusion or 7-nitro-indazole by daily int raperitoneal injection; control rats were given nutrient solution only and/or vehicles, Blood ethanol levels did not differ among the ethano l-treated groups. The amount of ethanol-dependent neuronal degeneratio n in the entorhinal cortex, dentate gyrus, and olfactory bulb glomerul i-visualized with the de Olmos cupric silver stain and quantitatively assessed in tile binge-intoxicated rats-was either unchanged or signif icantly increased by the NOS inhibitors, Although the efficacies of th e inhibitors cannot be directly compared because various NOS forms wer e probably inhibited to differing extents, the results do not support the idea that endogenous NO is a neurotoxic mediator of ethanol's effe cts. Rather, NO may have a modest neuroprotectant role in this model o f early brain damage induced by ethanol. In addition, the NOS that is localized histochemically as NADPH diaphorase was present primarily in regions and/or cells not damaged by binge ethanol treatment, Assuming that NADPH diaphorase represents most of the NO forming enzyme(s), th is suggests a transcellular mechanism for NO, A further observation wa s that hippocampal CA pyramidal neuron degeneration was extensive in r ats infused centrally with N-G-nitro-L-arginine methyl ester.