Monaminergic changes associated with audiogenic seizures in ethanol-dependent rats

1. A previous report demonstrated the efficacy of combining dopaminergic an d serotonergic agonists in suppressing audiogenic seizures induced in ethan ol-dependent rats undergoing withdrawal. Moreover, an increase in dopamine and a reduction in serotonin levels in the striatum were associated with su ch seizures. 2. The present study was designed to examine neurochemical changes in the s triatum associated with repeated episodes of ethanol withdrawal seizures in untreated ethanol-dependent rats as well as in those treated with amphetam ine and fenfluramine in combination. 3. Ethanol-dependent rats undergoing audiogenic seizures exhibited an incre ase 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 seizu res by reversing the neurochemical changes in the striatum in ethanol-depen dent rats. However, increased dopamine but decreased serotonin levels in th e striatum were observed in rats undergoing one episode of ethanol withdraw al, but not in those experiencing multiple episodes of ethanol withdrawal. 4. Thus, alterations in striatal dopamine and serotonin levels were, at bes t, necessary but not sufficient to predispose audiogenic seizure susceptibi lity in ethanol-dependent rats.