Daily dose of ethanol and the development and decay of acute and chronic tolerance and physical dependence in rats.
Using behavioral and physiological measures, we compared the rates of development and decay of acute and chronic tolerance to ethanol (ET) and the severity of the withdrawal syndrome. Male rats were treated with 6, 9, or 12 g/kg/day ET or equicaloric dextrin maltose, delivered intragastrically. Although treatment duration varied, the total dose of ET was kept constant at 162 g/kg/rat for the three groups. The effects of a cumulative test dose of ET or equicaloric dextrin maltose, after exposure to a total of 0, 42, 83, 126, and 162 g/kg ET, and at 3, 5, and 7 days after termination of the chronic treatments, were evaluated on rectal temperature, dowel performance, and tail-flick and startle responses. After the initial five tolerance tests, chronic treatments were discontinued and rats were tested in a modified open-field apparatus and for their startle response to an auditory stimulus at 8, 12, 16, 20, 32, and 40 h later. With all measures, little tolerance developed in the 6-g/kg/day group. On the other hand, development of chronic tolerance was fastest in rats treated with the 12-g/kg/dose of ET. Chronic tolerance did not develop to ET's depressant effect on the startle response. Acute tolerance declined with chronicity of treatment in animals given the largest daily dose of ET. During withdrawal, and in contrast to the dextrin maltose-treated animals, there was impairment in all measures taken during the modified open-field test and hypersensitivity of the startle response for all three chronic ET-treated animals. Greatest behavioral impairment occurred in animals treated with 12 g/kg/day, and some impairment was still evident 40 h after the last dose of ET. Thus, the severity of the withdrawal syndrome was greatest in the group displaying the most acute and chronic tolerance.
Pohorecky
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LA
Center of Alcohol Studies, Rutgers University, Piscataway, NJ 08855-0969.
Roberts
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P
D000435:Alcoholic Intoxication / Q000523:psychology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*; D013997:Time Factors
D000431:Ethanol