Acamprosate suppresses ethanol-induced place preference in mice with ethanol physical dependence

The present study investigated the effect of acamprosate on ethanol (etoh)-induced place preference in mice with etoh physical dependence. the expression of etoh (2 g/kg,intraperitoneally)-induced place preference in mice without etoh treatment before the experiment was dose-dependently suppressed by acamprosate. the levels of protein kinase a (pka) and phospho-camp response element binding protein (p-creb) in the limbic forebrain after etoh-conditioning in naïve mice was unchanged. furthermore,mice on the 4th day of withdrawal from continuous etoh vapor inhalation for 9 days showed transient and significant enhancement of etoh (1 g/kg,intraperitoneally)-induced place preference,which was significantly suppressed by acamprosate (300 mg/kg,oral administration; p.o.,once a day) administered daily for 3 days after withdrawal from etoh inhalation and during etoh-conditioning. pka and p-creb proteins in the limbic forebrain of etoh-conditioned mice on 4th day of withdrawal from continuous etoh inhalation for 9 days significantly increased,which were completely abolished by acamprosate. these findings suggest that the signal transduction pathway via the pka-p-creb pathway in the limbic forebrain may be functionally related to the development of sensitization of etoh-induced place preference and provide a possible molecular basis for the pharmacological effect of acamprosate to prevent or reduce the relapse of alcohol dependence. © the japanese pharmacological society.