Long-lasting tolerance to alcohol following a history of dependence.
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.
Rimondini
Roberto
R
Department of Pharmacology, University of Bologna, Italy. roberto.rimondini@unibo.it
Sommer
Wolfang H
WH
Dall'Olio
Rossella
R
Heilig
Markus
M
D000280:Administration, Inhalation; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D006993:Hypnotics and Sedatives / Q000097:blood / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007699:Kinesthesis / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects*; D004856:Postural Balance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D006993:Hypnotics and Sedatives; D000431:Ethanol