Novel synergistic treatment of ethanol withdrawal seizures in rats with dopamine and serotonin agonists.

A recent observation in this laboratory of a simultaneous increase in striatal dopamine and a decrease in serotonin in ethanol-dependent rats during ethanol withdrawal prompted studies with combined dopaminergic + serotoninergic agonists to stop withdrawal seizures. Amphetamine (2 mg/kg) + fenfluramine (8 mg/kg) given jointly, but not separately, prevented ethanol withdrawal seizures as effectively as benzodiazepines (chlordiazepoxide), the current drugs of choice. The combination of amphetamine and fenfluramine, unlike chlordiazepoxide, significantly reduced intake of ethanol during and immediately following ethanol withdrawal.