Ethanol effects on GABA-serotonin interactions in the Dorsal Raphe Nucleus

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DESCRIPTION (provided by applicant): Alcohol dependence is a serious disorder for which effective treatments are lacking. Dysregulation of the serotonin system has been widely implicated in alcohol dependence though little is known about chronic ethanol's effects on serotonin neurons themselves or the microcircuit to which they belong. In the dorsal raphe (DR), a midbrain structure from which 50% of the brain's serotonin arises, serotonin neuron activity is modulated by local GABA neurons. The effects of chronic ethanol on GABA neurons of the DR and their modulation of serotonin neuron activity have not been explored to date. Using whole-cell slice electrophysiology, chronic ethanol vapor exposure, behavioral, optogenetic and chemogenetic approaches, the goal of this proposal is to test the hypothesis that chronic ethanol induces adaptations in GABA neuron function within the DR, resulting in altered modulation of serotonin neuron activity. The results of the proposed experiments will provide insight into the role of DR GABA neurons in dysregulated serotonin activity resulting from chronic ethanol exposure and will inform the development of pharmacotherapies targeting the serotonin system for the treatment of alcoholism.