Acamprosate Decreases the Hypermotility During Repeated Ethanol Withdrawal

Abstract

One of the known behavioral actions of acamprosate is to prevent relapse in weaned alcoholics. However, the mechanism underlying this effect remains unclear. In this study, the motility of Wistar male rats, which were either alcoholized by ethanol inhalation or simultaneously alcoholized and treated orally by acamprosate (400 mg/kg/day) for 4 weeks, was measured during four episodes of the ethanol withdrawal. The concentrations of excitatory and inhibitory amino acids were also assayed by the microdialysis technique with OPA/BME precolumn derivatisation and electrochemical detection in the nucleus accumbens. Acamprosate reduces both the motility and the glutamate microdialysate content during the first 12 h of ethanol withdrawal in comparison to the alcoholized untreated group. The basal concentration of the sulfonated amino acid taurine increased significantly in alcoholized acamprosate-treated rats compared to alcoholized untreated rats. These results suggest that acamprosate is able to reduce the hypermotility during ethanol withdrawal syndrome directly by reducing the nucleus accumbens glutamate concentration or indirectly by increasing the taurine and GABA brain level.