A. Dahchour et al., CENTRAL EFFECTS OF ACAMPROSATE - PART-1 - ACAMPROSATE BLOCKS THE GLUTAMATE INCREASE IN THE NUCLEUS-ACCUMBENS MICRODIALYSATE IN ETHANOL WITHDRAWN RATS, PSYCHIATRY RESEARCH-NEUROIMAGING, 82(2), 1998, pp. 107-114
One of the known behavioral actions of acamprosate is to decrease hype
rmotility during alcohol withdrawal. However, the mechanism of this ef
fect remains unclear. In this study, the concentrations of excitatory
and inhibitory amino acids were assayed by the microdialysis technique
with OPA/BME precolumn derivatization and electrochemical detection i
n the nucleus accumbens of male Wistar rats which were either alcoholi
zed by ethanol inhalation or simultaneously alcoholized and treated or
ally by acamprosate (400 mg/kg/day) for 4 weeks. Without treatment, ex
tracellular glutamate increased during the withdrawal phase, while oth
er amino acids tested (aspartate, arginine, taurine, alanine and GABA)
remained stable. In contrast, the alcoholized rats treated with acamp
rosate failed to present the increase in glutamate during ethanol with
drawal, while other amino acids tested also remained stable. The obser
ved glutamate increase could be responsible for the hyperexcitability
observed during episodes of ethanol withdrawal. These results suggest
that acamprosate is able to reduce the ethanol withdrawal syndrome by
reducing the concentration of glutamate in the nucleus accumbens. (C)
1998 Elsevier Science Ireland Ltd. All rights reserved.