ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Changes in GABA(A) receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The trial behind it
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Who cites it
52 citing papers in PubMed, 125 citations in OpenAlex.
- Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.Psychopharmacology · 2013Trial
- Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence.Alcoholism, clinical and experimental research · 2011Trial
- Real-World Phenobarbital Use, Treatment Escalation, and Clinical Outcomes in Critically Ill Patients With Alcohol Withdrawal Syndrome: A Multicenter Propensity-Matched Cohort Study.Critical care explorations · 2026Observational
- Alcohol withdrawal and the sigma receptor: exploring the link between withdrawal and cognitive impairment.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- N6-methyladenosine RNA methylation is a novel epitranscriptomic regulator of excessive alcohol drinking and vulnerability to relapse.bioRxiv : the preprint server for biology · 2025Article
- Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome.Neuropsychopharmacology reports · 2023Article
- Putative roles for homeostatic plasticity in epileptogenesis.Epilepsia · 2023Review
- Proteomics and weighted gene correlated network analysis reveal glutamatergic synapse signaling in diazepam treatment of alcohol withdrawal.Frontiers in pharmacology · 2022Article
- Evaluation of a Phenobarbital-Based Protocol for Severe Alcohol Withdrawal in Critically Ill Patients.Hospital pharmacy · 2021Article
- Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study.Cureus · 2021Article
- Regulation of GABAInternational journal of molecular sciences · 2020Review
- α4βδ-GABAJournal of neuroscience research · 2018Article
- α4-GABAMolecular and cellular neurosciences · 2018Article
- Treatment of Severe Alcohol Withdrawal: A Focus on Adjunctive Agents.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2017Article
- Ethanol Exposure RegulatesThe Journal of pharmacology and experimental therapeutics · 2017Article
- Regulating the Efficacy of Inhibition Through Trafficking of γ-Aminobutyric Acid Type A Receptors.Anesthesia and analgesia · 2016Review
- Article
- Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons.Brain and behavior · 2015Article
- Chronic Intermittent Ethanol Regulates Hippocampal GABA(A) Receptor Delta Subunit Gene Expression.Frontiers in cellular neuroscience · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in the expression of subunits of the GABA type A (GABA(A)) receptor are implicated in the development of ethanol tolerance and dependence as well as in the central hyperexcitability associated with ethanol withdrawal. The impact of such changes on GABA(A) receptor function and pharmacological sensitivity was investigated with cultured rat hippocampal neurons exposed to ethanol for 5 d and then subjected to ethanol withdrawal. Both ethanol treatment and withdrawal were associated with a marked decrease in the maximal density of GABA-evoked Cl- currents, whereas the potency of GABA was unaffected. Ethanol exposure also reduced the modulatory efficacy of the benzodiazepine receptor agonists lorazepam, zolpidem, and zaleplon as well as that of the inverse agonists Ro 15-4513 and FG 7142, effects that were associated with a reduced abundance of mRNAs encoding the receptor subunits alpha1, alpha3, gamma2L, and gamma2S. Ethanol withdrawal restored the efficacy of lorazepam, but not that of low concentrations of zolpidem or zaleplon, to control values. Flumazenil, which was ineffective in control neurons, and Ro 15-4513 each potentiated the GABA response after ethanol withdrawal. These effects of withdrawal were accompanied by upregulation of the alpha2, alpha3, and alpha4 subunit mRNAs as well as of the alpha4 protein. Diazepam or gamma-hydroxybutyrate, but not baclofen, prevented the changes in both GABA(A) receptor pharmacology and subunit mRNA levels induced by ethanol withdrawal. Changes in GABA(A) receptor gene expression induced by prolonged exposure to and withdrawal of ethanol are thus associated with altered GABA(A) receptor function and pharmacological sensitivity.
Indexed as
Identifiers
14684873PMC6740939W1839802520What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.