Exposure to either acute or chronic ethanol alters the activity of hippocampal cholinergic neurons. Nuerochemical and electrophysiological measures of cellular activity are responsive to ethanol, and several effects of ethanol can be blocked or potentiated by drugs which modify central cholinergic activity. Further, long-lasting pathological changes have been observed in the hippocampus of animals chronically treated with ethanol for extended periods of time. In order to determine the direct effects of ethanol on hippocampal neurons, the proposed studies will examine the electrophysiological activity of an identified population of hippocampal cells, and will study the effects of acute and chronic ethanol exposure. This will be done by characterizing the spontaneous and evoked activity of cells in the hippocampal CA3 field and determining the effects of acute, systemic ethanol administration, both before and after chronic ethanol exposure, in an acute animal preparation. Local application of receptor agonists and antagonists will be performed to further characterize the observed population of cells, and will permit a determination of the effects of ethanol treatment on neuronal responsiveness. Various aspects of the development and dissipation of tolerance, of progressive changes in neuronal activity with continuing ethanol exposure, of changes in activity during withdrawal from chronic ethanol, and of the presence of residual, long-lasting effects of chronic ethanol will also be investigated. These studies should provide a greater understanding of the central effects of ethanol on a defined cell population and of the specific neuronal alterations which accompany chronic ethanol exposure and the development of tolerance to ethanol.
