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Journal article
Experimental Traumatic Brain Injury Alters Ethanol Consumption and Sensitivity
Journal of neurotrauma, v 31(20), pp 1700-1710
15 Oct 2014
PMID: 24934382
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine-and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal dopaminergic neurotransmission while altering ethanol consumption. Examining TBI effects on ethanol responsitivity will improve our understanding of alcohol use post-TBI in humans.
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Details
- Title
- Experimental Traumatic Brain Injury Alters Ethanol Consumption and Sensitivity
- Creators
- Jennifer L. Lowing - Wayne State UniversityLaura L. Susick - Wayne State UniversityJames P. Caruso - Wayne State UniversityAnthony M. Provenzano - Wayne State UniversityRamesh Raghupathi - Drexel UniversityAlana C. Conti - Neurosurgery
- Publication Details
- Journal of neurotrauma, v 31(20), pp 1700-1710
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 11
- Grant note
- Wayne State University (WSU) Department of Neurosurgery Children's Hospital of Michigan Foundation WSU Office of the Vice President for Research (ACC)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000342302200003
- Scopus ID
- 2-s2.0-84908004908
- Other Identifier
- 991019167859704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences