Monoaminergic changes associated with audiogenic seizures in ethanol-dependent rats

1. A previous report demonstrated the efficacy of combining dopaminergic and serotonergic agonists in suppressing audiogenic seizures induced in ethanol-dependent rats undergoing withdrawal. Moreover, an increase in dopamine and a reduction in serotonin levels in the striatum were associated with such seizures. 2. The present study was designed to examine neurochemical changes in the striatum associated with repeated episodes of ethanol withdrawal seizures in untreated ethanol-dependent rats as well as in those treated with amphetamine and fenfluramine in combination. 3. Ethanol-dependent rats undergoing audiogenic seizures exhibited an increase in striatal dopamine and a reduction in striatal serotonin as compared to control and ethanol-dependent rats not undergoing seizures. Amphetamine and fenfluramine in combination effectively suppressed the audiogenic seizures by reversing the neurochemical changes in the striatum in ethanol-dependent rats. However, increased dopamine but decreased serotonin levels in the striatum were observed in rats undergoing one episode of ethanol withdrawal, but not in those experiencing multiple episodes of ethanol withdrawal. 4. Thus, alterations in striatal dopamine and serotonin levels were, at best, necessary but not sufficient to predispose audiogenic seizure susceptibility in ethanol-dependent rats.