The overall goal of this research program is to develop clinically relevant electrophysiological measures in animals in order to explore the neurobehavioral mechanisms underlying alcohol intoxication and addiction. A generally accepted theory of alcoholism posits that genetically influenced risk factors interact with both environmental """"""""stressors"""""""" as well as the neuroadaptive changes that occur during heavy drinking to produce the final outcome we define as the alcoholism phenotype. This research program has used animal models of alcohol drinking that incorporate several crucial aspects of human alcoholism to explore hypotheses related to this theory. These models include: lines of mice and rats selected for enhanced alcohol preference, alcohol self-administration models that allow for the separation of appetitive and consumptive behaviors, and models incorporating chronic exposure to alcohol vapors. One new and highly promising approach to identifying electrophysiological phenotypes for the study of alcoholism is the use of event-related oscillations (EROs). The proposed studies will use EROs and pre-pulse inhibition of the acoustic startle response (PPI/ASR) to further the study of alcohol consumption and chronic alcohol exposure in these models. Our studies have focused on the stress-related neuropeptide systems Neuropeptide Y, (NPY), Corticotropin releasing factor, (CRF) as being crucial in the understanding individual responses to alcohol intoxication, alcohol preference, and neuroadaption to alcohol exposure. The proposed studies will also employ neurochemical techniques to aid in the localization and co-localization of content/message of NPY and CRF and their receptors in specific brain sites, such as the extended amygdala, hippocampus and hypothalamus in our models. Taken together these studies will allow for the development of clinically relevant brain measures of risk for and the consequences of alcohol consumption as well as to identify animal models that will allow these measures to be used to explore the brain mechanisms underlying addiction liability to alcohol.
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