Overview: Molecular and Cellular Pathogenesis in Alcoholism. The UNC NIAAA Alcohol Research Center (ARC) fosters interdisciplinary collaborative research on alcoholism, alcohol abuse and the impact of alcohol on health and disease - exactly the goal of an NIAAA ARC. The UNC Bowles Center for Alcohol Studies (CAS) provides a foundation of administrative support and dedicated space for alcohol research. Across ARC components molecular signaling, synaptic networks, neurocircuitry and psychopathology are investigated in models of binge drinking. The scope of these studies requires the Center mechanism to integrate the multiple signaling systems and neurocircuits that underlie complex addiction-like behaviors. The UNC ARC is a catalyst of discovery that promotes collaboration, expands use of new methods and scientific knowledge through regular research meetings, scientific seminars, core research services, annual clinical conferences, pilot projects and through stimulation of interest in the effects of alcohol on health across the University and State. Training and mentoring of students and junior faculty contribute to scholarly interactions and successful laboratory research programs through the ARC. Health professional and youth curricula promote interest in science and knowledge that contribute to improved health. The ARC synergizes with existing investigator funding to promote interactions among multidisciplinary investigators focused on molecular mechanisms of ethanol-related behavioral and tissue pathology. The ARC Specific Aims are to investigate mechanisms of alcohol-induced behavioral, molecular, cellular and neural circuit pathogenesis and to disseminate information on alcohol to health professionals and youth. Research components investigate hypotheses on ethanol-induced regulation of signaling kinases, receptor expression and trafficking, cytokine and peptide gene induction, changes in brain networks and circuitry as well as alcohol induced mood, behavior and drug taking as addiction-like behavioral pathologies. By conducting focused investigations that integrate molecular signaling mechanisms across neural networks and neurocircuitry, the ARC creates synergies that promote and catalyze discoveries. This ARC proposal continues a research focus on molecular and cellular mechanisms with a new emphasis on dysfunctional brain networks and neurocircuitry, a theme at the cutting edge of neuroscience. The ARC will conduct, promote, support, and mentor research on alcoholic pathology and educate broad groups of health professionals and youth in North Carolina.

Public Health Relevance

Alcoholism is a major public health problem of unknown etiology. This ARC is devoted to understanding the mechanisms of pathology associated with alcoholism and alcohol abuse. The field has been hampered by lack of understanding of the brain circuitry that underlies alcohol-induced pathology. We propose a comprehensive and integrated investigation of molecular, cellular and circuit pathology in alcoholism using forefront strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
4P60AA011605-19
Application #
8975098
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Grandison, Lindsey
Project Start
1997-12-01
Project End
2017-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
19
Fiscal Year
2016
Total Cost
Indirect Cost
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
Jaramillo, Anel A; Randall, Patrick A; Stewart, Spencer et al. (2018) Functional role for cortical-striatal circuitry in modulating alcohol self-administration. Neuropharmacology 130:42-53
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
Fiorenza, Amanda M; Shnitko, Tatiana A; Sullivan, Kaitlin M et al. (2018) Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue. Alcohol Clin Exp Res 42:1051-1061
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 :
Faccidomo, Sara; Swaim, Katarina S; Saunders, Briana L et al. (2018) Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice. Psychopharmacology (Berl) 235:1681-1696
Bohnsack, John Peyton; Hughes, Benjamin A; O'Buckley, Todd K et al. (2018) Histone deacetylases mediate GABAA receptor expression, physiology, and behavioral maladaptations in rat models of alcohol dependence. Neuropsychopharmacology 43:1518-1529
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
Fish, E W; Wieczorek, L A; Rumple, A et al. (2018) The enduring impact of neurulation stage alcohol exposure: A combined behavioral and structural neuroimaging study in adult male and female C57BL/6J mice. Behav Brain Res 338:173-184
Beattie, Matthew C; Reguyal, Christopher S; Porcu, Patrizia et al. (2018) Neuroactive Steroid (3?,5?)3-hydroxypregnan-20-one (3?,5?-THP) and Pro-inflammatory Cytokine MCP-1 Levels in Hippocampus CA1 are Correlated with Voluntary Ethanol Consumption in Cynomolgus Monkey. Alcohol Clin Exp Res 42:12-20

Showing the most recent 10 out of 227 publications