Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats.

Thirty adult male Wister rats were pretrained to criterion on the moving belt test, and then made tolerant to ethanol by daily administration of increasing doses over a period of 3 weeks. After a one-month recovery period, they were divided into 3 groups, subjected to bilateral frontal polar cortical ablations, sham-operation and no operation respectively. After postoperative recovery, the cycle of ethanol treatment and testing was repeated. Only the lesioned group failed to reacquire tolerance. A pilot experiment showed that occipital cortical ablations also prevented tolerance. In a second experiment 32 rats, which had similarly undergone and then recovered from an initial period of ethanol tolerance, were divided into 4 groups which received daily treatment with sucrose plus cycloheximide (0.3 mg/kg), sucrose plus saline, ethanol plus cycloheximide, and ethanol plus saline respectively. Only the ethanol plus saline group re-acquired tolerance. Tt is concluded that frontal polar cortical lesions and cycloheximide can both block the development of tolerance to ethanol in animals previously shown to be capable of developing such tolerance.