The purpose of this application is to develop a Consortium for the initiative "Neurobiology of Adolescent Drinking in Adulthood" (NADIA). The NADIA will coordinate a diverse group of basic neuroscientists in a multidisciplinary research project to clearly define the persistent effects of adolescent alcohol exposure on adults, and to begin to explore the neurobiological mechanisms. The overarching hypothesis of this consortium is that models of human underage drinking will impact brain maturation resulting in persistent changes in adult brain function and structure that relate to changes in behavior. This NADIA will use adolescent intermittent ethanol (AIE) rat models that mimic episodic human adolescent underage drinking. Multiple research components will integrate molecular, cellular, physiological, endocrine, genetic neuroanatomical and behavioral studies utilizing cutting edge and novel approaches to investigate potential long term consequences of human underage drinking. An abundance of evidence suggests that during adolescence, cognition, affect, and reward driven behavioral repertoires are uniquely plastic and responsive to environmental influences. Maturation of brain circuitry that underlies motivation, affect and decision making are expected to be sensitive to ethanol disruption, resulting in increased adult psychopathology. This consortium will integrate investigators that share common hypotheses and overlapping protocols. Each will contribute to an improved understanding of the consequences of adolescent alcohol exposure on brain physiology, structure, chemistry, maturation and behavioral induces of affect, motivation, social functioning, decision-making cognitive assessments, impulsivity, circadian rhythms, and alcohol drinking behaviors using AIE. Components cover broad inter-related investigations of the neurocircuitry between frontal-cortical, striatal, hippocampal, extended amygdala and hypothalamic nuclei as well as hormonal maturation of hypothalamic-adrenal interactions across gender, providing a broad global investigation of the development of neural networks that underlie maturation of complex behaviors. The scientific core will provide components with brain MRI-DTI (brain volume - structure), brain regional histology-immunohistochemistry and establish a data repository for future brain network analysis. Understanding the impact of underage drinking on adult neurobiology is important to guide public health initiatives.

Public Health Relevance

Drinking in adolescence is common but the consequences of excessive drinking during adolescence are unknown. This proposal will establish a consortium of investigators to determine the consequences of adolescent alcohol exposure on brain physiology, structure, chemistry, maturation and behavioral indices of affect, motivation and/or cognition. This information will be important to guide public health policy and develop better tools for the prevention of risky behavior in adolescents.

National Institute of Health (NIH)
Resource-Related Research Projects--Cooperative Agreements (U24)
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Special Emphasis Panel (ZAA1)
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Noronha, Antonio
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Zou, Jian Y; Crews, Fulton T (2014) Release of neuronal HMGB1 by ethanol through decreased HDAC activity activates brain neuroimmune signaling. PLoS One 9:e87915
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Qin, Liya; Liu, Yuxin; Hong, Jau-Shyong et al. (2013) NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration. Glia 61:855-68
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