Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice.
Autor: | Athanason AC; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA., Nadav T; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Cates-Gatto C; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Roberts AJ; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Roberto M; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Varodayan FP; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA.; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. |
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Jazyk: | angličtina |
Zdroj: | Neurobiology of stress [Neurobiol Stress] 2023 Apr 27; Vol. 24, pp. 100542. Date of Electronic Publication: 2023 Apr 27 (Print Publication: 2023). |
DOI: | 10.1016/j.ynstr.2023.100542 |
Abstrakt: | Hyperkateifia and stress-induced alcohol cravings drive relapse in individuals with alcohol use disorder (AUD). The brain stress signal norepinephrine (also known as noradrenaline) tightly controls cognitive and affective behavior and was thought to be broadly dysregulated with AUD. The locus coeruleus (LC) is a major source of forebrain norepinephrine, and it was recently discovered that the LC sends distinct projections to addiction-associated regions suggesting that alcohol-induced noradrenergic changes may be more brain region-specific than originally thought. Here we investigated whether ethanol dependence alters adrenergic receptor gene expression in the medial prefrontal cortex (mPFC) and central amgydala (CeA), as these regions mediate the cognitive impairment and negative affective state of ethanol withdrawal. We exposed male C57BL/6J mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and assessed reference memory, anxiety-like behavior and adrenergic receptor transcript levels during 3-6 days of withdrawal. Dependence bidirectionally altered mouse brain α1 and β receptor mRNA levels, potentially leading to reduced mPFC adrenergic signaling and enhanced noradrenergic influence over the CeA. These brain region-specific gene expression changes were accompanied by long-term retention deficits and a shift in search strategy in a modified Barnes maze task, as well as greater spontaneous digging behavior and hyponeophagia. Current clinical studies are evaluating adrenergic compounds as a treatment for AUD-associated hyperkatefia, and our findings can contribute to the refinement of these therapies by increasing understanding of the specific neural systems and symptoms that may be targeted. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.) |
Databáze: | MEDLINE |
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