title: Juvenile Traumatic Brain Injury Increases Alcohol Consumption and Reward in Female Mice.
abstract: Traumatic brain injury (TBI) is closely and bi-directionally linked with alcohol use, as by some estimates intoxication is the direct or indirect cause of one-third to one-half of all TBI cases. Alcohol use following injury can reduce the efficacy of rehabilitation and increase the chances for additional injury. Finally, TBI itself may be a risk factor for the development of alcohol use disorders. Children who suffer TBIs have poorer life outcomes and more risk of substance abuse. We used a standardized closed-head injury to model mild traumatic brain injuries. We found that mice injured as juveniles but not during adulthood exhibited much greater alcohol self-administration in adulthood. Further, this phenomenon was limited to female mice. Using behavioral testing, including conditioned place preference assays, we showed that early injuries increase the rewarding properties of alcohol. Environmental enrichment administered after injury reduced axonal degeneration and prevented the increase in drinking behavior. Additionally, brain-derived neurotrophic factor gene expression, which was reduced by TBI, was normalized by environmental enrichment. Together, these results suggest a novel model of alterations in reward circuitry following trauma during development.
authors.affiliation: 1 Department of Neuroscience and Group in Behavioral Neuroendocrinology, the Ohio State University Wexner Medical Center , Columbus, Ohio.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weil
authors.affiliation: 1 Department of Neuroscience and Group in Behavioral Neuroendocrinology, the Ohio State University Wexner Medical Center , Columbus, Ohio.
authors.forename: Kate
authors.initials: K
authors.lastname: Karelina
authors.affiliation: 1 Department of Neuroscience and Group in Behavioral Neuroendocrinology, the Ohio State University Wexner Medical Center , Columbus, Ohio.
authors.forename: Kristopher R
authors.initials: KR
authors.lastname: Gaier
authors.affiliation: 1 Department of Neuroscience and Group in Behavioral Neuroendocrinology, the Ohio State University Wexner Medical Center , Columbus, Ohio.
authors.forename: Timothy E D
authors.initials: TE
authors.lastname: Corrigan
authors.affiliation: 2 Department of Physical Medicine and Rehabilitation, the Ohio State University Wexner Medical Center , Columbus, Ohio.
authors.forename: John D
authors.initials: JD
authors.lastname: Corrigan
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000523:psychology* / Q000639:trends*; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000523:psychology*; D003213:Conditioning, Psychological / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D012201:Reward; D012646:Self Administration
keywords: BDNF; alcohol; development; environmental enrichment; sex differences; traumatic brain injury