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Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood
Open accessAbstract
Binge drinking is common during adolescence and can lead to the development of psychiatric disorders, including alcoholism in adulthood. Here, the role and persistent effects of histone modifications during adolescent intermittent ethanol (AIE) exposure in the development of anxiety and alcoholism in adulthood were investigated. Rats received intermittent ethanol exposure during post-natal days 28-41, and anxiety-like behaviors were measured after 1 and 24 h of the last AIE. The effects of AIE on anxiety-like and alcohol-drinking behaviors in adulthood were measured with or without treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). Amygdaloid brain regions were collected to measure HDAC activity, global and gene-specific histone H3 acetylation, expression of brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated (Arc) protein and dendritic spine density (DSD). Adolescent rats displayed anxiety-like behaviors after 24 h, but not 1 h, of last AIE with a concomitant increase in nuclear and cytosolic amygdaloid HDAC activity and HDAC2 and HDAC4 levels leading to deficits in histone (H3-K9) acetylation in the central (CeA) and medial (MeA), but not in basolateral nucleus of amygdala (BLA). Interestingly, some of AIE-induced epigenetic changes such as, increased nuclear HDAC activity, HDAC2 expression, and decreased global histone acetylation persisted in adulthood. In addition, AIE decreased BDNF exons I and IV and Arc promoter specific histone H3 acetylation that was associated with decreased BDNF, Arc expression and DSD in the CeA and MeA during adulthood. AIE also induced anxiety-like behaviors and enhanced ethanol intake in adulthood, which was attenuated by TSA treatment via normalization of deficits in histone H3 acetylation of BDNF and Arc genes. These novel results indicate that AIE induces long-lasting effects on histone modifications and deficits in synaptic events in the amygdala, which are associated with anxiety-like and alcohol drinking behaviors in adulthood.
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“alcohol use during adolescence might lead to epigenetic modifications that alter amygdalar gene expression and dendritic density, increasing susceptibility to anxiety-like behaviours and alcohol ingestion in adulthood.140”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [140]
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“For example, AAE can lead to long-lasting histone modifications that alter synaptic function in the amygdala and likely contributes anxiety-like behavior [50].”
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“For example, AAE can lead to long-lasting histone modi fi cations that alter synaptic function in the amygdala and likely contributes anxiety-like behavior [50].”
Background
Metadata
- Authors
- Pandey, S. C., Sakharkar, A. J., Tang, L., & Zhang, H.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Pandey, Subhash C.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 82
- Pages
- 607-619
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC4581895
- OpenAlex
- W1997141979
- Cited by
- 191
- References
- 68
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 17 · 2022: 18 · 2021: 24 · 2020: 18 · 2019: 25 · 2018: 15 · 2017: 16 · 2016: 19 · 2015: 6
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-019971)
- AA-010005
- AA-013341
- Department of Veterans Affairs (I01BX000143)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adolescent intermittent ethanol exposure, binge drinking, histone modifications, histone H3 acetylation, histone deacetylase, trichostatin A, amygdala, anxiety-like behavior, alcoholism, alcohol consumption, brain-derived neurotrophic factor, Arc protein, dendritic spine density, central amygdala, medial amygdala, epigenetic modifications, synaptic plasticity
- MeSH terms
- Underage Drinking, Acetylation, Ethanol, Alcoholism, Animals, Anxiety Disorders, Brain, Central Nervous System Depressants, Cytoskeletal Proteins, Disease Models, Animal, Histones, Hydroxamic Acids, Male, Nerve Tissue Proteins, Gene Expression, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Binge Drinking
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