Abstract
In this study we examined whether nitric oxide (NO) expression in various areas of the rat brain is affected in a model of ethanol dependency. We compared the effects of ethanol administered in single or repetitive doses (by oral gavage and ad libitum) on NO concentration the brain, in the presence and absence of intraperitoneally-injected NO synthase (NOS) inhibitors N G-nitro-L-arginine methyl ester (L-NAME) and 7 nitroindazole (7-NI) . NO was quantified by detecting NO2-, using a NO2-/ NO3- assay kit. The NO levels were significantly higher with repetitive ethanol administration, compared to saline-administered controls, in all parts of the rat brain. The NO levels in the brains of rats given single doses of ethanol were significantly greater than in controls, except in the hypothalamus. These differences were reduced by treatment with 7 NI (a selective nNOS inhibitor) . We conclude that ethanol administration increases NO levels in the rat brain, and that these increases are mainly produced by nNOS. We propose that elevated NO levels in the hypothalamus, which are particularly marked with repetitive ethanol administration, activate the hypothalamic-pituitary-adrenal axis, resulting in the development of alcohol dependence.
