The overall goal of this research program is to utilize electrophysiological measures, specifically waking EEG, event-related potentials (ERPs), and measures of sleep EEG to explore the neural substrates which underlie alcohol's abuse liability. Studies in both human and animal models suggest that factors such as: a low level of response to alcohol, anxiety traits, and cognitive/personality variables can moderate risk for the development of alcoholism in humans and perhaps also influence alcohol preference in animals. In addition to these genetic/familial risk factors, individuals must be exposed to periods of heavy drinking to actually develop alcohol use disorders. Heavy drinking can cause persistent neuroadaptive changes in neurochemistry, electrophysiology, and behaviors which contribute to the addiction process. Thus, it is our hypothesis that preexisting genetically influenced risk factors interact with the neuroadaptive changes that occur following chronic alcohol exposure to produce the final outcome we define as the alcoholism phenotype. We have developed well defined animal """"""""correlates"""""""" of human electrophysiological measures associated with alcoholism such as the P300 component of the ERP. Electrophysiological studies have been conducted in outbred strains as well as ethanol preferring (P) and non-preferring (NP) rats in order to characterize genetically influenced variables in an animal model of voluntary ethanol consumption. The current proposal includes an evaluation of replicate lines of high alcohol drinking (HAD1, HAD2) and low alcohol drinking (LAD 1, LAD 2) rats, as well as replicate lines of mouse strains that differ in ethanol consumption (LAP 1, LAP 2, HAP 1,HAP 2). The newly proposed studies will also use electrophysiological measures to further the functional activity of specific brain sites, such as the extended amygdala, during ethanol consumption. Neuropharmacological studies will be aimed at further understanding neuropeptide modulation of alcohol consumption as well as the effects of ethanol exposure on measures of electrophysiology and alcohol consumption. The use of these electrophysiological measures, combined with neurochemical findings will provide data necessary to directly link these peptidergic systems to alcohol preference and long term neuroadaptation to alcohol.
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