Characterizing the Edinger-Westphal response to alcohol

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The overall goal of this proposal is to characterize the response of the Edinger-Westphal nucleus (EW) to alcohol. It has been shown in our lab and others that EW is robustly responsive to alcohol by various routes of administration. Because EW is a prominent target for alcohol administration, the proposed studies are intended to elucidate its mechanism and role in alcohol intoxication. The specific aims of this proposal are: 1) to characterize the neurochemistry of EW response to alcohol administration, 2) to identify candidate neurotransmitter receptors mediating activation of EW cells following alcohol administration, and 3) to identify behavioral effects of EW microinjected receptor antagonists blocking activation of EW. Neurochemistry will be analyzed using immunohistochemical and in situ techniques. Identification of receptors will involve the systemic administration of various receptor antagonists and subsequent analysis of EW activation by immunohistochemical analysis of c-Fos. Several common behavioral assays (i.e. alcohol sensitivity measures, locomotor activity, and anxiety measures) will be used to assess the role of EW neural activity following alcohol administration. It is hypothesized that activation of EW is targeted to a specific subset of neurons that are activated by specific receptor subtypes. It is further hypothesized that activation of these neurons is involved in the generation of alcohol-induced behavioral effects. The findings of this proposal will be important in understanding the mechanistic role of EW activation and its involvement in behaviors associated with intoxication. Furthermore, this investigation will aid in the pursuit of pharmacological treatments for alcoholism.