The benzodiazepine antagonist Ro 15-1788 does not antagonize the ethanol withdrawal syndrome

It has been suggested that the signs and symptoms of the ethanol withdrawal syndrome may be due to the increased production of an "inverse agonist" that binds to the central benzodiazepine (BZ) recognition site in the brain. Ro 15-1788 (a potent antagonist at the central BZ recognition site), diazepam, and Ro 15-1788 plus diazepam were administered to groups of rats undergoing overt ethanol withdrawal. Ro 15-1788 did not alter the severity of the ethanol withdrawal reactions, but antagonized the ameliorative effect of diazepam. The results of our studies suggest that (1) the ethanol withdrawal syndrome is not produced by an endogenous ligand acting on the central BZ recognition site, and (2) diazepam decreases the severity of the ethanol withdrawal syndrome, at least in part, by its action at the central BZ recognition site.