Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.
The purpose of the present study was to determine the acute effects of the anticraving compound acamprosate (calcium acetylhomotaurinate) and the closely related compound homotaurine on ethanol intake and ethanol-stimulated dopamine release in the nucleus accumbens. Male rats were treated with acamprosate (200 or 400 mg/kg intraperitoneally, i.p.) or homotaurine (10, 50, or 100 mg/kg i.p.) 15 min prior to access to 10% ethanol and water for 1 h in a two-bottle choice restricted access paradigm. A separate group of rats was implanted with microdialysis probes in the nucleus accumbens and given an acute injection of ethanol (1.5 g/kg i.p.) that was preceded by saline, acamprosate, or homotaurine. Acamprosate and homotaurine dose-dependently reduced ethanol intake and preference. These compounds also delayed or suppressed ethanol-stimulated increases in nucleus accumbens dopamine release, suggesting that acamprosate and homotaurine may reduce ethanol intake by interfering with the ability of ethanol to activate the mesolimbic dopamine reward system.
Olive
M Foster
MF
Ernest Gallo Clinic and Research Center, UCSF Department of Neurology, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA. folive@itsa.ucsf.edu
Nannini
Michelle A
MA
Ou
Christine J
CJ
Koenig
Heather N
HN
Hodge
Clyde W
CW
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D013654:Taurine; D000431:Ethanol; C001355:tramiprosate; D000077443:Acamprosate; D004298:Dopamine