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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24AA020024-03
Application #
8317287
Study Section
Special Emphasis Panel (ZAA1-DD (11))
Program Officer
Noronha, Antonio
Project Start
2010-09-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$433,133
Indirect Cost
$140,476
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Vetreno, Ryan P; Lawrimore, Colleen J; Rowsey, Pamela J et al. (2018) Persistent Adult Neuroimmune Activation and Loss of Hippocampal Neurogenesis Following Adolescent Ethanol Exposure: Blockade by Exercise and the Anti-inflammatory Drug Indomethacin. Front Neurosci 12:200
Broadwater, Margaret A; Lee, Sung-Ho; Yu, Yang et al. (2018) Adolescent alcohol exposure decreases frontostriatal resting-state functional connectivity in adulthood. Addict Biol 23:810-823
Coleman Jr, Leon G; Zou, Jian; Qin, Liya et al. (2018) HMGB1/IL-1? complexes regulate neuroimmune responses in alcoholism. Brain Behav Immun 72:61-77
Coleman Jr, Leon G; Crews, Fulton T (2018) Innate Immune Signaling and Alcohol Use Disorders. Handb Exp Pharmacol 248:369-396
Walter, Thomas Jordan; Vetreno, Ryan P; Crews, Fulton T (2017) Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects. Alcohol Clin Exp Res 41:2066-2081
Walter, T Jordan; Crews, Fulton T (2017) Microglial depletion alters the brain neuroimmune response to acute binge ethanol withdrawal. J Neuroinflammation 14:86
Vetreno, Ryan P; Patel, Yesha; Patel, Urvi et al. (2017) Adolescent intermittent ethanol reduces serotonin expression in the adult raphe nucleus and upregulates innate immune expression that is prevented by exercise. Brain Behav Immun 60:333-345
Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz et al. (2017) Adult rat cortical thickness changes across age and following adolescent intermittent ethanol treatment. Addict Biol 22:712-723
Crews, Fulton T; Walter, T Jordan; Coleman Jr, Leon G et al. (2017) Toll-like receptor signaling and stages of addiction. Psychopharmacology (Berl) 234:1483-1498
Coleman Jr, Leon G; Zou, Jian; Crews, Fulton T (2017) Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7. J Neuroinflammation 14:22

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