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UNC Alcohol Research Center

MOLECULAR AND CIRCUIT PATHOGENESIS OF ALCOHOL ADDICTION

Overview and Goals

This NIAAA Alcohol Research Center (ARC) Grant is the catalytic element that integrates a large group of investigators across the University of North Carolina at Chapel Hill (UNC). The UNC School of Medicine, Bowles Center for Alcohol Studies (BCAS), provides a foundation of administrative support and dedicated Bowles building space for alcohol research. The UNC ARC fosters interdisciplinary collaborative research on alcohol use disorders, alcohol abuse and the impact of alcohol on health and disease – exactly the goal of an NIAAA ARC. The ARC has facilitated the growth and development of UNC into an outstanding alcohol research University, among the best in the world. Research and education have always centered on a theme of molecular and cellular pathology in alcohol use disorders. This renewal focuses on the molecular mechanisms that underlie alcohol-induced circuit pathology across the stages of addiction. Ultimately, our guiding hypothesis is that alcohol-induced dysregulation of neural circuitry drives pathological behaviors and is thus the key cause of all alcohol-related pathology.

This 4th renewal of the UNC ARC continues an emphasis on alcohol use disorder pathology, integrating existing and new faculty. More specifically, the proposed studies in this ARC renewal will investigate changes in neural circuits and molecular signaling in models of drinking across the proposed stages of addiction1 . We will broadly test the conceptual model that altered signaling in discrete neural circuits drives specific pathological behaviors associated with discrete models of alcohol exposure. The scope of these studies addresses the critical neurobiological changes leading to all alcoholic pathologies, i.e. the mechanisms leading to heavy chronic drinking. The ARC integrates multiple signaling systems and neurocircuits that each focus on specific mechanisms within and across brain regions. The research components will also include the translational endpoint, resting state functional magnetic resonance imaging (rsfc-MRI) assessments within and across each component’s hypothesized pathological circuit. This is critical, as it provides the means to move detailed mechanistic studies of brain circuits beyond rodents. This approach is expected to increase discovery, improve models and gain strength from common assessments across preclinical models to the ARC human studies. This ARC renewal continues to be the catalytic element that integrates a broad group of investigators, pairing faculty within ARC components that promote discovery across the BCAS and UNC.

 

The following Specific Aims guide and integrate the overall efforts of this ARC:

 

  1. To investigate mechanisms of alcohol-induced pathogenesis of Alcohol Use Disorder and Addiction. This proposal connects principal investigators of involving 15 independent funded faculty. By design, each research component of this ARC will focus on specific models that capture distinct endophenotypes associated with alcohol abuse. A range of molecular mechanisms that drive these circuit alterations will be explored, including kinases, cytokines and neuropeptides. By conducting focused investigations that integrate neurocircuitry and molecular signaling mechanisms across brain regions, the ARC creates synergies that promote and catalyze discoveries.

 

  1. To disseminate information on alcohol to the public, youth, adolescents and health professionals. The ARC leads the state in alcohol education efforts. To have the greatest impact on health, the ARC informs practicing health professionals, health professional students and youth through specific curricula for each group.

 

This ARC proposal continues a research focus on pathogenesis of alcohol addiction with emphasis on molecular and circuit mechanisms that lead to dysfunctional brain networks, a theme at the cutting edge of neuroscience. The ARC will conduct, promote, support, and mentor research on the pathology of alcohol use disorders and educate broad groups of the public, including health professionals, families, college students and youth in North Carolina on the causes and prevention of these disorders.