Deconstructing the role of central nucleus of the amygdala neurotensin neurons in alcohol reward and intoxication

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DESCRIPTION (provided by applicant): Alcohol use disorders have an enormous societal and fiscal impact in the United States. Moreover, alcohol is the third leading cause of preventable death (Mokdad et al., 2004). Elucidating the neuronal circuitry that contributes to the rewarding properties of alcohol may provide insight into therapeutic mechanisms for treating alcohol use disorders. The central nucleus of the amygdala (CeA) has been shown to play a role in regulating various aspects of alcohol drinking behavior, however, the CeA is a heterogeneous nucleus where different genetically defined populations may contribute to ethanol related behaviors in different ways. This proposal aims to assess the causal role of CeA-neurotensin (NTS) neurons in mediating ethanol intoxication and self-administration using cutting edge tools. I will perform immunohistochemical, behavioral and electrophysiological experiments. In particular I will investigate the projection to the parabrachial nuclei (PBN) in the hindbrain, a region that is thought to play a major role in stress and anxiety. Through this research I plan to show that CeA-NTS neurons that project to the PBN are activated in response to alcohol and associated cues and mediate some of the rewarding properties of alcohol. These experiments will uncover new neuronal circuitry and mechanisms that may contribute to alcohol use disorders and allow for future targets for the treatment of this pathology.