Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice
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 coerul...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289523000309 |
| _version_ | 1797812047384150016 |
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| author | A.C. Athanason T. Nadav C. Cates-Gatto A.J. Roberts M. Roberto F.P. Varodayan |
| author_facet | A.C. Athanason T. Nadav C. Cates-Gatto A.J. Roberts M. Roberto F.P. Varodayan |
| author_sort | A.C. Athanason |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T07:32:45Z |
| format | Article |
| id | doaj.art-a8afb873a98b44e7ac39b7a928738b5e |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-03-13T07:32:45Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-a8afb873a98b44e7ac39b7a928738b5e2023-06-04T04:24:03ZengElsevierNeurobiology of Stress2352-28952023-05-0124100542Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male miceA.C. Athanason0T. Nadav1C. Cates-Gatto2A.J. Roberts3M. Roberto4F.P. Varodayan5Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADevelopmental 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; Corresponding author. Department of Psychology, Binghamton University-SUNY, S4-175G, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA.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.http://www.sciencedirect.com/science/article/pii/S2352289523000309AlcoholAnxiety-like behaviorCentral amygdala (CeA)Medial prefrontal cortex (mPFC)Noradrenaline/norepinephrine |
| spellingShingle | A.C. Athanason T. Nadav C. Cates-Gatto A.J. Roberts M. Roberto F.P. Varodayan Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice Neurobiology of Stress Alcohol Anxiety-like behavior Central amygdala (CeA) Medial prefrontal cortex (mPFC) Noradrenaline/norepinephrine |
| title | Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| title_full | Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| title_fullStr | Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| title_full_unstemmed | Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| title_short | Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| title_sort | chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice |
| topic | Alcohol Anxiety-like behavior Central amygdala (CeA) Medial prefrontal cortex (mPFC) Noradrenaline/norepinephrine |
| url | http://www.sciencedirect.com/science/article/pii/S2352289523000309 |
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