Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat.
Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.
Spanagel
R
R
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Hölter
S M
SM
Allingham
K
K
Landgraf
R
R
Zieglgänsberger
W
W
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D000427:Alcohol Deterrents; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate