THE ANTI-CRAVING DRUG ACAMPROSATE REDUCES C-FOS EXPRESSION IN RATS UNDERGOING ETHANOL WITHDRAWAL

Acamprosate (Ca salt of N-acetylhomotaurine) is a novel anti-craving s ubstance which a double-blind placebo-controlled study has proven to b e therapeutically useful in the prevention of relapses in weaned alcoh olics. In the present study the expression of the immediate-early gene c-Sos in rat hippocampal and cerebellar neurons was used to monitor t he modulatory effect of acamprosate on neuronal excitability during et hanol withdrawal. Several hybridization techniques were employed to in vestigate the effect of acamprosate on c-Sos expression. Acamprosate ( 200 mg/kg; intraperitoneally) reduced the elevated c-Sos mRNA levels i n the hippocampus and the cerebellum following 24 h of ethanol withdra wal, or the application of the convulsant pentylenetetrazole. The effe ct of ethanol withdrawal on c-Sos expression was more pronounced in th e cerebellum than in the hippocampus. In the hippocampus (CA1) and the cerebellum acamprosate alone induced a significant increase in c-fos expression in drug-naive animals. Only in the hippocampus did co-admin istration of pentylenetetrazole during ethanol withdrawal induce a fur ther increase in c-Sos expression. The present findings support the no tion that acamprosate elicits its preventive effect on relapse by redu cing the hyperexcitability of central neurons during withdrawal, follo wing long-term ethanol consumption.