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THE EFFECT OF DIAZEPAM ON VOLUNTARY ETHANOL INTAKE IN A RAT MODEL OF ALCOHOLISM
Authors:HEDLUND, LARS   WAHLSTROM, GORAN
Affiliation:Department of Pharmacology, Umeå University S-901 87 Umeå, Sweden
Abstract:This paper reports the effects of a diazepam treatment on voluntaryethanol intake in rats included in an animal model of alcoholism.In a first dose-seeking experiment, rats had a choice between10% (w/v) ethanol and water for 24 h each week. Single dosesof diazepam between 2 and 20 mg/kg injected i.p. prior to the24-h choice caused a dose-dependent decrease in voluntary ethanolintake from 3.2±0.4 g/kg/day down to 2.3±0.3 g/kg/day(P<0.01) after a dose of 20 mg/kg. In a second experiment,psychological dependence was induced by a 1-year intermittentexposure to ethanol (a choice between 10% ethanol and waterfor 24 h each week, followed by an i.p. injection of 2.0 g/kgof ethanol). After this year, the rats were given a continuouschoice between ethanol and water. A 3-week treatment with diazepam(20 mg/kg/day, i.p.) was started in week 68, during which perioda choice of 10% (w/v) ethanol was available only on the firstand the last days of treatment. On the first day of the diazepamtreatment, ethanol intake was decreased from a pre-experimentalvalue of 2.7±0.3 g/kg/day to 1.2±0.1 g/kg/day(P<0.001). On the last day of the treatment, voluntary intakewas higher than before the treatment (3.8±0.27 g/kg/day,P<0.01). Ethanol intake remained elevated during the weekafter the end of the diazepam treatment (P<0.05). When singledoses of diazepam (20 mg/kg) were re-tested 10 and 19 weeksafter the treatment, there was no decrease in ethanol intake,indicating that the initial effect had not been re-established.
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