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1 Department of Pharmacology, University of Toronto, and Alcoholism and Drug Addiction Research Foundation of Ontario, Toronto, Ontario, Canada
Adult male Wistar rats, trained to stay on a continuous motor-driven belt running over an electrified grid, showed a dose-dependent impairment of this learned performance when given ethanol in amounts which produced blood alcohol levels ranging from 75 to 350 mg/100 ml. After 14 daily doses of ethanol, rising from 3 to 6 g/kg, the treated animals showed a parallel shift of dose-response curve, such that the ED5O had increased by approximately 33%. Sucrose-treated controls showed no such shift. By 14 days after cessation of alcohol treatment, the dose-response curve of the alcohol-treated animals had returned to its starting position. In a second experiment, the change in dose-response curve was examined at 3-day intervals during a 24-day treatment period and a subsequent 28-day recovery period. Tolerance was maximally increased in three weeks of treatment; it was appreciably reduced within one week of withdrawal, appeared to be subnormal for a short time and returned to normal within three to four weeks after cessation of the daily alcohol administration. Blood ethanol measurements in the first experiment indicate that the changes in tolerance resulted from changes in resistance of the nervous system, rather than in alcohol distribution. Development of increased tolerance was accompanied by the appearance of signs of hyperirritability after the peak effect of each test dose had passed.
Submitted on August 12, 1968
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