ArticlePloS one2012
Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder.Frontiers in synaptic neuroscience · 2022Review
- GABAAlcoholism, clinical and experimental research · 2019Article
- Role of GABAMolecular brain · 2017Review
- Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice.Alcoholism, clinical and experimental research · 2016Article
- Candidate gene-environment interaction research: reflections and recommendations.Perspectives on psychological science : a journal of the Association for Psychological Science · 2015Review
- Effect of GABRA2 genotype on development of incentive-motivation circuitry in a sample enriched for alcoholism risk.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Neural basis of benzodiazepine reward: requirement for α2 containing GABAA receptors in the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking.Psychopharmacology · 2014Article
- The Genetics, Neurogenetics and Pharmacogenetics of Addiction.Current behavioral neuroscience reports · 2014Article
- Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition.Nature communications · 2013Article
- Risky Business: Pathways to Progress in Biologically Informed Studies of Psychopathology.Psychological inquiryArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchanged.
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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.