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Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats

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Abstract

Rats were treated by intragastric intubation of a 20% ethanol solution in doses of 9–15 g/kg in 3–5 fractions for 1–7 days. Both tolerance and physical dependence were demonstrated after this treatment with the maximum tolerable doses to only a few days. Tolerance was assessed by signs of severity of intoxication: coma, loss of righting reflex, ataxia-3, ataxia-2, ataxia-1, sedation, and neutrality. During withdrawal, as blood ethanol concentrations approached 100 mg/dl the ethanol dependence phase was characterized by the onset of signs and responses of progressive severity: hyperactivity, tremors, spastic rigidity, and spontaneous convulsive seizures. A significant degree of tolerance was demonstrated for all signs of intoxication after 4 days of treatment, but did not reach maximum level even after 7 days. The severity of the withdrawal reactions intensified progressively to a maximum intensity after 4 days of treatment when as many as 72% of animals exhibited severe withdrawal signs and reactions including convulsive seizures. These different time courses suggest that tolerance and physical dependence are mediated through different mechanisms.

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Authors and Affiliations

  1. L.A.R., National Institute on Alcohol Abuse and Alcoholism, WAW Bldg, 2700 M.L. King Jr. Ave., S.E., 20032, Washington, D.C., USA

    Edward Majchrowicz

  2. Neurobiology Department, Armed Forces Radiobiology Research Institute, 20014, Bethesda, Maryland, USA

    Walter A. Hunt

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  1. Edward Majchrowicz
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  2. Walter A. Hunt
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Majchrowicz, E., Hunt, W.A. Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats. Psychopharmacology 50, 107–112 (1976). https://doi.org/10.1007/BF00430477

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  • DOI: https://doi.org/10.1007/BF00430477

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