title: Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.
abstract: Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.
authors.affiliation: Neuroscience and Behavior Program and Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, Massachusetts 01003.
authors.forename: Wanette M
authors.initials: WM
authors.lastname: Vargas
authors.affiliation: Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, Massachusetts 01003.
authors.forename: Lynn
authors.initials: L
authors.lastname: Bengston
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, and.
authors.forename: Nicholas W
authors.identifier: http://orcid.org/0000-0001-8901-8917
authors.initials: NW
authors.lastname: Gilpin
authors.affiliation: Department of Public Health, University of Massachusetts, Amherst, Massachusetts 01003.
authors.forename: Brian W
authors.identifier: http://orcid.org/0000-0002-8646-5823
authors.initials: BW
authors.lastname: Whitcomb
authors.affiliation: Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, Massachusetts 01003, hrichardson@cns.umass.edu.
authors.forename: Heather N
authors.identifier: http://orcid.org/0000-0001-7659-1212
authors.initials: HN
authors.lastname: Richardson
mesh_terms: D000367:Age Factors; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D063425:Binge Drinking / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D066127:White Matter / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000431:Ethanol
keywords: adolescent; alcohol; binge; dependence; myelin; prefrontal