Evidence for parallel development of tolerance to the hyperactivating and discoordinating effects of ethanol

Rats maintained on diets containing 6.5% ethanol or equicaloric sucrose solutions were challenged at weekly intervals with 1.5 or 2.0 g/kg ethanol or isotonic saline 14 h after withdrawal from the diet. Tolerance developed to both the hyperactivating (increased line crossings and time active) and discoordinating (disrupted rotarod performance) effects of the 1.5 g/kg dose of ethanol, but was less obvious with the 2.0 g/kg dose. Chlorpromazine (2.5 mg/kg) had a greater depressant effect in animals chronically treated with ethanol, suggesting that some alterations in the functioning of noradrenergic and/or dopaminergic systems may accompany chronic ethanol treatment. However, amphetamine and propranolol did not appear to affect ethanol- and sucrose-treated rats differently. The present studies have therefore shown a parallel development of tolerance to the discoordinating and hyperactivating effects of ethanol and have implicated an underlying noradrenergic and/or dopaminergic mechanism, although the precise nature of the mechanism has not been clarified.