Citation

Lowing JL, Susick LL, Caruso JP, Provenzano AM, Raghupathi R, Conti AC. J. Neurotrauma 2014; 31(20): 1700-1710.

Affiliation

Wayne State University, Neurosurgery, Detroit, Michigan, United States ; jlowing@med.wayne.edu.

Copyright

(Copyright © 2014, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2013.3286

PMID

24934382

Abstract

Altered alcohol consumption patterns following 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 study, was to describe histological and behavioral outcomes of a non-contusive 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 d, after TBI. At 14 d post-TBI, when mice were tested for ethanol sensitivity following acute high-dose ethanol (4 g/kg, i.p.), brain-injured mice exhibited increased sedation time compared to uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 d post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 d of consumption was significantly reduced in TBI mice compared to 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.

Language: en