Acutely ethanol, has tension-reducing (anxiolytic) properties, whereas chronic ethanol, administered to the point of dependence, induces anxiety particularly during withdrawal. Both of these actions may contribute to the motivational effects important for the development and maintenance of ethanol abuse. Previous work in our laboratory has established sensitive measures for the anti-conflict and dependence-producing actions of ethanol. Neuropharmacological studies have provided evidence for a role of GABA, serotonin and corticotropin-releasing factor (CRF) in these anti-conflict and dependence-inducing effects of ethanol, and neurobiological sites for the effects of ethanol on anxiety substrates may involve the amygdala. The purpose of the present proposal will be to continue to explore the neurobiological basis for the anti-conflict (""""""""anxiolytic"""""""") and dependence-inducing effects of ethanol. Emphasis will be placed on determining the brain sites of interaction of ethanol with GABA, serotonin and CRF. Studies will also be directed at exploring a possible role of neural and adrenal steroids and sex differences in those effects of ethanol. The anti-conflict effects of acute ethanol will be measured in a Geller-Seifter conflict test sensitive to ethanol. Ethanol withdrawal will be measured with three automated tests: The elevated plus maze, as an index of """"""""anxiety""""""""; the acoustic startle response as a measure of """"""""arousal""""""""; and a """"""""tremor response"""""""" as a quantifiable measure of physical withdrawal. Confirmation of brain site specific neurochemical interactions with ethanol will be made with in vivo microdialysis in awake, freely moving animals exposed to acute or chronic ethanol. Results derived from these studies will go far towards identifying specific neurochemical brain systems of critical importance for the development and maintenance of ethanol abuse and alcoholism.
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