The effects of atropine on the tolerance and the convulsions seen after withdrawal from forced barbital drinking in the rat

Abstract

Male rats were forced to drink a barbital solution as their only drinking fluid for 33 weeks. During the last part of the treatment the average dose of barbital was around 200 mg/kg/day. In the abstinence period after barbital treatment, tolerance was recorded with a hexobarbital anaesthesia threshold utilizing an EEG criterium. Convulsions were recorded in jiggle cages. On days 3 and 28 of the abstinence period, i.p. pretreatment with atropine (2, 4, and 8 mg/kg) was given 1.5 h before threshold determinations. The barbital treatment induced a clear tolerance to the hexobarbital, which still could be detected on day 28 of abstinence. Atropine (8 mg/kg) reduced the hexobarbital threshold in tolerant and in control animals at both the time of maximum tolerance (day 3) and later during abstinence (day 28). The magnitude of the response was greater in tolerant animals, but no parallel shift in the dose-response curve was seen. The convulsions during abstinence were reduced for at least 8 h after atropine treatment (8mg/kg) on day 3. These results support the hypothesis that cholinergic mechanisms are involved in the changes induced by chronic barbiturate treatments.