Reversal of alcohol-induced amnesia by the benzodiazepine inverse agonist Ro 15-4513.
We investigated the effects of benzodiazepine inverse agonists on ethanol-induced amnesia using a passive avoidance task. Pretraining treatment of mice with ethanol significantly impaired the passive avoidance response: there was a significant reduction in the % retention and step-down latency. The benzodiazepine inverse agonists, Ro 15-4513 and beta-CCM, significantly increased the % retention and prolonged the step-down latencies in mice treated with ethanol, but FG 7142 did not. The anti-amnesic effects of Ro 15-4513 were completely antagonized by co-administration of Ro 15-1788, a benzodiazepine antagonist. These results suggest that the anti-amnesic effect of Ro 15-4513 on alcohol-induced amnesia is mediated by benzodiazepine receptors.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Tohyama
K
K
Kameyama
T
T
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001386:Azides / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D051379:Mice; D013997:Time Factors
D001386:Azides; D002243:Carbolines; D001569:Benzodiazepines; C026072:1-methyl-beta-carboline-3-carboxylic acid; D000431:Ethanol; D005442:Flumazenil; C042957:Ro 15-4513