The benzodiazepine receptor inverse agonist RO15-4513 exacerbates, but does not precipitate, ethanol withdrawal in mice.
RO15-4513, an imidazobenzodiazepine that has been reported to antagonize several behavioral and biochemical actions of ethanol, was given to C3H mice at various times during withdrawal from chronic (72 hours) continuous exposure to ethanol vapor. When administered immediately following chronic ethanol exposure, RO15-4513 (6 or 12 mg/kg) did not influence the withdrawal response. However, when given at subsequent times (3, 5, and 8 hours postethanol withdrawal), RO15-4513 significantly increased the severity of the withdrawal response in ethanol-exposed mice. Moreover, this exacerbation was completely reversed by pretreatment with the benzodiazepine receptor antagonist RO15-1788. Thus, these data indicate that the benzodiazepine inverse agonist, RO15-4513, is capable of exacerbating, but not precipitating, ethanol withdrawal.
Becker
H C
HC
Veterans Administration Medical Center, Charleston, SC.
Anton
R F
RF
D000161:Acoustic Stimulation / Q000009:adverse effects; D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome
D000345:Affinity Labels; D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513