ArticleAlcoholism, clinical and experimental research2018
Histone Deacetylase Inhibitor Suberanilohydroxamic Acid Treatment Reverses Hyposensitivity to γ-Aminobutyric Acid in the Ventral Tegmental Area During Ethanol Withdrawal.
Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.INNOSC theranostics & pharmacological sciences · 2024Article
- Transcriptional Dysregulation of Cholesterol Synthesis Underlies Hyposensitivity to GABA in the Ventral Tegmental Area During Acute Alcohol Withdrawal.Biological psychiatry · 2024Article
- Targeting Epigenetic Mechanisms to Treat Alcohol Use Disorders (AUD).Current pharmaceutical design · 2021Article
- KCNK13 potassium channels in the ventral tegmental area of rats are important for excitation of ventral tegmental area neurons by ethanol.Alcoholism, clinical and experimental research · 2021Article
- Histone modifications, DNA methylation, and the epigenetic code of alcohol use disorder.International review of neurobiology · 2021Article
- Epigenetic mechanisms underlying pathobiology of alcohol use disorder.Current pathobiology reports · 2020Article
- Early Life Stress- and Drug-Induced Histone Modifications Within the Ventral Tegmental Area.Frontiers in cell and developmental biology · 2020Review
- Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.Behavioral neuroscience · 2019Article
- The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alleviates depression-like behavior and normalizes epigenetic changes in the hippocampus during ethanol withdrawal.Alcohol (Fayetteville, N.Y.) · 2019Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe ventral tegmental area (VTA) is important for alcohol-related reward and reinforcement. Mouse VTA neurons are hyposensitive to γ-aminobutyric acid (GABA) during ethanol (EtOH) withdrawal, and GABA responsiveness is normalized by in vitro treatment with histone deacetylase inhibitors (HDACi). The present study examined the effect of a systemically administered HDACi, suberanilohydroxamic acid (SAHA) on GABA sensitivity, and related molecular changes in VTA neurons during withdrawal after chronic EtOH intake in rats.
methodsSprague Dawley male adult rats were fed with Lieber-DeCarli diet (9% EtOH or control diet) for 16 days. Experimental groups included control diet-fed and EtOH diet-fed (0- or 24-hour withdrawal) rats treated with either SAHA or vehicle injection. Single-unit recordings were used to measure the response of VTA neurons to GABA. Immunohistochemistry was performed to examine levels of HDAC2, acetylated histone H3 lysine 9 (acH3K9), and GABA
resultsVTA neurons from the withdrawal group exhibited GABA hyposensitivity. In vivo SAHA treatment 2 hours before sacrifice normalized the sensitivity of VTA neurons to GABA. EtOH withdrawal was associated with increased HDAC2 and decreased acH3K9 protein levels; SAHA treatment normalized acH3K9 levels. Interestingly, no significant change was observed in the mRNA levels of HDAC2. The mRNA levels, but not protein levels, of GABA
conclusionsWithdrawal from chronic EtOH exposure results in a decrease in GABA-mediated inhibition, and this GABA hyposensitivity is normalized by in vivo SAHA treatment. Disruption of signaling in the VTA produced by alteration of GABA neurotransmission could be 1 neuroadaptive physiological process leading to craving and relapse. These results suggest that HDACi pharmacotherapy with agents like SAHA might be an effective treatment for alcoholism.
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