Long-lasting tolerance to alcohol following a history of dependence

Addict Biol. 2008 Mar;13(1):26-30. doi: 10.1111/j.1369-1600.2007.00079.x.

Abstract

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.

MeSH terms

  • Administration, Inhalation
  • Alcoholism / physiopathology*
  • Animals
  • Arousal / drug effects
  • Dose-Response Relationship, Drug
  • Drug Tolerance
  • Ethanol / blood
  • Ethanol / toxicity*
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / toxicity*
  • Injections, Intraperitoneal
  • Kinesthesis / drug effects*
  • Male
  • Metabolic Clearance Rate / physiology
  • Motor Skills / drug effects*
  • Postural Balance / drug effects*
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Hypnotics and Sedatives
  • Ethanol