Acamprosate and alcohol: II. Effects on alcohol withdrawal in the rat.
The suppressing effect of acamprosate (calcium-acetyl homotaurinate) on alcohol drinking is well established; however, little is known about its effects upon the alcohol-induced withdrawal syndrome. Male Wistar rats received as a sole drinking fluid a 20% (v/v) alcohol solution for one week. Animals consumed on average 5.3 +/- 0.3 g/kg per day alcohol, which resulted in blood alcohol levels of 38 +/- 14 mg/dl. For the quantification of alcohol withdrawal we used a new radio-telemetric system which enabled us to monitor body temperature, locomotor activity, food and water intake patterns constantly during alcohol withdrawal. Although alcohol intake and the resulting blood alcohol levels were low, clear signs of withdrawal could be observed. Thus, hyperthermia and hyperlocomotion occurred 18 h after the termination of forced alcohol drinking. Food intake was initially enhanced but dropped significantly below basal food intake in control animals one day after the termination of forced alcohol drinking. Acamprosate given twice a day (200 mg/kg, i.p., 8 a.m. and 8 p.m.) reduced hyperlocomotion and food intake significantly in the alcohol withdrawal animals, however, it did not change withdrawal-induced hyperthermia. When acamprosate was given to alcohol-naive animals, it increased locomotor activity and body temperature transiently, in particular during the rats' active night phase. In summary, (i) the radio-telemetric system used in the present study proved to be a very sensitive method for quantifying alcohol-induced withdrawal symptoms; (ii) acamprosate reduced alcohol-induced physical signs of withdrawal, however, this effect could not be observed for all parameters measured, which might be explained by the fact that (iii) acamprosate exerts a slight, transient psychomotor stimulant effects by itself.
Spanagel
R
R
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Putzke
J
J
Stefferl
A
A
Schöbitz
B
B
Zieglgänsberger
W
W
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000427:Alcohol Deterrents; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate