THE 5-HT3 ANTAGONIST MDL-72222 EXACERBATES ETHANOL WITHDRAWAL SEIZURES IN MICE

Ethanol-dependent mice were treated with the 5-HT3 antagonist MDL 7222 2 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10 , and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after wit hdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display a ny seizures. Treatment with another 5-HT3 antagonist, ICS 205-930 (23 and 46 mg/kg), or the 5-HT2 receptor antagonist ketanserin, did not af fect ethanol withdrawal seizures. The findings suggest MDL 72222 selec tively enhances sensitivity to withdrawal seizures following chronic e thanol exposure.