title: Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.
abstract: Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, Chapel Hill, NC 27599-7178, United States. Electronic address: leon_coleman@med.unc.edu.
authors.forename: Leon Garland
authors.initials: LG
authors.lastname: Coleman
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, Chapel Hill, NC 27599-7178, United States. Electronic address: wen_liu@med.unc.edu.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, Chapel Hill, NC 27599-7178, United States; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: ipek@cs.unc.edu.
authors.forename: Ipek
authors.initials: I
authors.lastname: Oguz
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: styner@cs.unc.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, Chapel Hill, NC 27599-7178, United States; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: ftcrews@med.unc.edu.
authors.forename: Fulton T
authors.initials: FT
authors.lastname: Crews
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016326:Extracellular Matrix Proteins; D000431:Ethanol
keywords: Alcohol; Behavioral flexibility; Extracellular matrix; MRI; Neurocan; Underage drinking