Chronic ethanol exposure selectively increases diazepam-insensitive [3H]RO15-4513 binding in mouse cerebellum.
The effect of chronic ethanol exposure and withdrawal on [3H]RO15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][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 (Bmax) 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 GABAA receptor subtype may play some role in ethanol dependence and withdrawal.
Becker
H C
HC
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, 29425 USA.
Jarvis
M F
MF
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001386:Azides / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
D001386:Azides; D018757:GABA Modulators; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513; D003975:Diazepam