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Long-lasting tolerance to alcohol following a history of dependence

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Tolerance to alcohol effects is one of the defining features of clinical alcohol dependence. Here, we hypothesized that the post-dependent state may include tolerance to sedative-hypnotic alcohol actions. To address this question, we used a recently developed animal model in which repeated cycles of alcohol intoxication and withdrawal trigger long-lasting behavioral plasticity. This animal model shares important features with the clinical condition. Animals were exposed to 7 weeks of intermittent alcohol vapor, allowed to recover for 3 weeks, and tested in protracted abstinence to exclude contributions from acute withdrawal. Post-dependent and control rats were injected with a hypnotic dose of alcohol (3 g/kg), and the loss of righting reflex (LORR) was recorded, blood alcohol levels were monitored, and the elimination rate was calculated. Post-dependent animals showed a decrease in LORR. Alcohol metabolism and elimination kinetics did not differ between groups. In conclusion, a history of alcohol dependence induces long-lasting hypnotic tolerance. This process may play an important role in maintaining the dependent state.
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Keywords: Alcohol; alcoholism; animal model; loss of righting reflex; rat; tolerance

Document Type: Research Article

Affiliations: 1: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA 2: Department of Pharmacology, University of Bologna, Italy and

Publication date: 2008-03-01

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