ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Reduced sedation and increased ethanol consumption in knock-in mice expressing an ethanol insensitive alpha 2 subunit of the glycine receptor.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- GutGut microbes · 2026Article
- A Role for Glycine Transporter-2 Inhibitors in Regulating Accumbal Dopamine Levels and Voluntary Alcohol Intake in Rats.Alcohol, clinical & experimental research · 2026Article
- Synaptic vs. Non-Synaptic Glycine Receptors: Physiological Role and Implications in Alzheimer's Disease Pathology.International journal of molecular sciences · 2026Review
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Changes in the Properties of Ethanol-Sensitive Molecular Targets During Maturation and Aging.Advances in experimental medicine and biology · 2025Review
- Changes in ethanol effects in knock-in mice expressing ethanol insensitive alpha1 and alpha2 glycine receptor subunits.Life sciences · 2024Article
- Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model.Progress in neurobiology · 2024Article
- Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals.iScience · 2023Article
- Overexpression of wild type glycine alpha 1 subunit rescues ethanol sensitivity in accumbal receptors and reduces binge drinking in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Aging in nucleus accumbens and its impact on alcohol use disorders.Alcohol (Fayetteville, N.Y.) · 2023Review
- Glycine Receptor Subtypes and Their Roles in Nociception and Chronic Pain.Frontiers in molecular neuroscience · 2022Review
- Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice.British journal of pharmacology · 2021Article
- Modulatory Actions of the Glycine Receptor β Subunit on the Positive Allosteric Modulation of Ethanol in α2 Containing Receptors.Frontiers in molecular neuroscience · 2021Article
- Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Previous studies have shown the presence of several subunits of the inhibitory glycine receptor (GlyR) in the reward system, specifically in medium spiny neurons (MSNs) of the nucleus Accumbens (nAc). It was suggested that GlyR α1 subunits regulate nAc excitability and ethanol consumption. However, little is known about the role of the α2 subunit in the adult brain since it is a subunit highly expressed during early brain development. In this study, we used genetically modified mice with a mutation (KR389-390AA) in the intracellular loop of the GlyR α2 subunit which results in a heteromeric α2β receptor that is insensitive to ethanol. Using this mouse model denoted knock-in α2 (KI α2), our electrophysiological studies showed that neurons in the adult nAc expressed functional KI GlyRs that were rather insensitive to ethanol when compared with WT GlyRs. In behavioral tests, the KI α2 mice did not show any difference in basal motor coordination, locomotor activity, or conditioned place preference compared with WT littermate controls. In terms of ethanol response, KI α2 male mice recovered faster from the administration of ataxic and sedative doses of ethanol. Furthermore, KI α2 mice consumed higher amounts of ethanol in the first days of the drinking in the dark protocol, as compared with WT mice. These results show that the α2 subunit is important for the potentiation of GlyRs in the adult brain and this might result in reduced sedation and increased ethanol consumption.
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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.