The effects of ethanol, phenobarbital, and baclofen on ethanol withdrawal in the rhesus monkey.

Abstract

Physical dependence on ethanol was produced in four rhesus monkeys by IV ethanol administration every 8 h. Ethanol was administered on each occasion until the eyeblink reflex was lost. Evidence of physical dependence development, in the form of tremoring 8 h after an infusion, appeared on day 8 of chronic administration. Abrupt cessation of ethanol administration following 16 days of chronic administration was accompanied by moderate to severe tremoring, retching, vomiting, and one or more convulsions. Peak withdrawal occurred between 12 and 32 h after abrupt discontinuation of ethanol administration, and decreased over a period of 64-204 h. Ethanol dependence was then reinstated. Once every 3-4 days, ethanol was withheld for 16 h. Withdrawal signs were scored for the first 12 h of this period, and then a test dose of ethanol, phenobarbital, or baclofen was administered. Withdrawal or intoxication signs were scored over the next 4 h, at which time ethanol administration was resumed. Both ethanol and phenobarbital suppressed ethanol withdrawal signs in a dose-related manner, and produced dose-related intoxication. Baclofen was largely ineffective in reducing withdrawal-induced tremors, although it was capable of producing sedation of a different type than that produced by phenobarbitol and ethanol.