CHRONIC ETHANOL EXPOSURE SELECTIVELY INCREASES DIAZEPAM-INSENSITIVE [H-3] RO15-4513 BINDING IN MOUSE CEREBELLUM

The effect of chronic ethanol exposure and withdrawal on [H-3]RO15-451 3 4H-imidazo[1,5a][1,4]benzodiazepine-3-carboxylate) binding to diazep am-sensitive and diazepam-insensitive binding sites was determined in mouse brain. Neither chronic ethanol treatment nor withdrawal signific antly altered total [H-3]R015-4513 binding in mouse cortex or cerebell um. However, diazepam-insensitive [H-3]R015-4513 binding density (B-ma x) in cerebellum was significantly increased immediately following chr onic ethanol treatment (60%) and at 8 h following withdrawal (75%). [H -3]R015-4513 binding affinity was not significantly influenced by chro nic ethanol exposure or withdrawal. These results indicate that chroni c ethanol treatment and withdrawal can selectively up-regulate diazepa m-insensitive [H-3]R015-4513 binding sites and suggest that this uniqu e GABA(A) receptor subtype may play some role in ethanol dependence an d withdrawal.