This component proposes to use a complementary neuroanatomical approach to behavioral genomics. While behavioral genomics proposes to identify genes involved in the development of alcoholism, this component proposes to identify brain regions important for development of this disease. Mapping of inducible transcription factors (ITFs) in brain has been applied to identify brain region-selective effects of ethanol administration on neural activity. However, early studies were able only to map ITF expression in brain after animals were administered this drug by an experimenter. Recently, mapping of ITFs has been successfully applied to identify brain regions changing their activity during voluntary self administration in mice. Four brain regions responding to alcohol consumption were identified: the core of nucleus accumbens, the media portion of central nucleus of amygdala, the Edinger-Westphal nucleus and the dentate gyrus. The main goal of the proposed project is to elucidate the specific relation of activity in the identified brain structures to alcohol consumption. We propose to achieve this goal by analysis ITF expression during acquisition of self-administration behavior, by dose- response analysis of ITF expression during alcohol self-administration, and by analysis of changes in ITF expression during reinstatement of alcohol self-administration in mice. These studies will be will be followed by characterization of molecular nature of ITF responses to alcohol self-administration in the identified brain regions. Furthermore, the previously identified brain regions might not be the only ones involved alcohol self-administration. Therefore, a second goal of this project is to identify additional structures involved in alcohol self- administration This goal will be achieved by investigating the time- course of ITF expression after alcohol consumption, and by analysis of """"""""alcohol craving""""""""-mediated changes in ITF expression. Identification of brain regions involved in self-administration of ethanol will provide clues to mechanisms mediating this behavior in humans, an understanding without which scientifically based treatment of alcoholism would be difficult to achieve.
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