Dextromethorphan attenuates ethanol withdrawal syndrome in rats

The effects of dextromethorphan (DM), a noncompetitive antagonist of the N- methyl-D-aspartate (NMDA) receptors, have been investigated on ethanol with drawal signs in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM (10, 20: and 40 mg/kg) and saline were injected intraperit oneally at the third hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also administered to ethanol naive rats. DM (40 mg/kg ) did not produce any significant change in locomotor activity in ethanol n aive rats. The effects of DM on locomotor activity and total ethanol withdr awal score were evaluated at the fourth and sixth hours of ethanol withdraw al. DM inhibited locomotor hyperactivity at these periods. DM also reduced total ethanol withdrawal score from the fourth hour to the sixth hour, and it significantly decreased audiogenic seizures. Seizure susceptibility afte r chronic ethanol exposure may be dependent upon sensitization or upregulat ion of NMDA processes and NMDA receptors. Our results suggest that inhibiti on of NMDA receptors by DM alleviates signs of ethanol withdrawal. (C) 1999 Elsevier Science, Inc.