Alcoholism and alcohol abuse are major health problems and represent a tremendous financial burden on our society. A growing literature indicates that chronic alcohol exposure leads to an imbalance between central stress and anti-stress systems in key brain circuits that regulate emotional behavior. These imbalances can lead to pathological behavior, including increased anxiety, stress-responsivity and enhanced risk of relapse. Despite these advances identifying the role these systems play in alcohol related behaviors, there remains a gap in our knowledge of the fundamental biological, cellular and circuit mechanisms that contribute to this dysregulated behavior. In order to more effectively treat alcohol abuse, it is necessary to define the impact of chronic alcohol exposure on the in the circuitry that is critical for regulation of this behavior. Here, we propose to characterize the impact of chronic alcohol exposure on anti-stress systems, specifically neuropeptide Y (NPY) and GABAergic neuroactive steroids, in the amygdala and extended amygdala, brain regions critical for regulation of stress and anxiety-like behavior. Additionally, we will utilize inducible channel rhodopsin viruses in combination with neurochemically specific Cre-recombinase driver lines to determine the impact of chronic alcohol exposure on GABAergic circuits in these brain regions. In total, the proposed work will begin to define specific alcohol-induced cellular and circuit adaptations that are likely to play key roles in pathological behaviors associated with alcoholism.
The focus of this project is to understand how alcohol exposure alters emotional behavior. Successful completion of this project will result in a greater understanding of how alcohol changes brain function. Further, these studies may provide insight as to how to develop more useful treatments for alcoholism and anxiety disorders.
|Hwa, Lara S; Neira, Sofia; Pina, Melanie M et al. (2018) Predator odor increases avoidance and glutamatergic synaptic transmission in the prelimbic cortex via corticotropin-releasing factor receptor 1 signaling. Neuropsychopharmacology :|
|Mazzone, C M; Pati, D; Michaelides, M et al. (2018) Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior. Mol Psychiatry 23:143-153|
|Yu, Waylin; Hwa, Lara S; Makhijani, Viren H et al. (2018) Chronic inflammatory pain drives alcohol drinking in a sex-dependent manner for C57BL/6J mice. Alcohol :|
|Jury, Nicholas J; Radke, Anna K; Pati, Dipanwita et al. (2018) NMDA receptor GluN2A subunit deletion protects against dependence-like ethanol drinking. Behav Brain Res 353:124-128|
|McHenry, Jenna A; Otis, James M; Rossi, Mark A et al. (2017) Hormonal gain control of a medial preoptic area social reward circuit. Nat Neurosci 20:449-458|
|Radke, Anna K; Jury, Nicholas J; Kocharian, Adrina et al. (2017) Chronic EtOH effects on putative measures of compulsive behavior in mice. Addict Biol 22:423-434|
|Hwa, Lara; Besheer, Joyce; Kash, Thomas (2017) Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective. F1000Res 6:298|
|Navarro, Montserrat; Olney, Jeffrey J; Burnham, Nathan W et al. (2016) Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli. Neuropsychopharmacology 41:1505-12|
|Crowley, Nicole A; Bloodgood, Daniel W; Hardaway, J Andrew et al. (2016) Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit. Cell Rep 14:2774-83|
|Hardaway, J Andrew; Jensen, Jennifer; Kim, Michelle et al. (2016) Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating. Behav Brain Res 307:25-34|
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