Abstract
The effect of chronic ethanol exposure and withdrawal on [ 3H]RO15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4 H-imidazo[1,5 a][1,4]benzodiazepine-3-carboxylate) binding to diazepam-sensitive and diazepam-insensitive binding sites was determined in mouse brain. Neither chronic ethanol treatment nor withdrawal significantly altered total [ 3H]RO15-4513 binding in mouse cortex or cerebellum. However, diazepam-insensitive [ 3H]RO15-4513 binding density ( B max) in cerebellum was significantly increased immediately following chronic ethanol treatment (60%) and at 8 h following withdrawal (75%). [ 3H]RO15-4513 binding affinity was not significantly influenced by chronic ethanol exposure or withdrawal. These results indicate that chronic ethanol treatment and withdrawal can selectively up-regulate diazepam-insensitive [ 3H]RO15-4513 binding sites and suggest that this unique GABA A receptor subtype may play some role in ethanol dependence and withdrawal.
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