ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
A Pharmacogenetic 'Restriction-of-Function' Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Development of Novel Pegylated Imidazobenzodiazepines Targeting α5 GABAA Receptors for Anxiety: A Comparative Prodrug and Metabolite Study.ACS chemical neuroscience · 2026Article
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- Peripheral cyclical expression of GABA-A receptor subunit genes and menstrual cycle affective change: a dimensional, transdiagnostic study.Translational psychiatry · 2025Article
- Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents.Biological psychiatry global open science · 2025Article
- Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways.ChemistryOpen · 2025Article
- Relaxin family peptide receptor 3 (RXFP3) expressing cells in the zona incerta/lateral hypothalamus augment behavioural arousal.Journal of neurochemistry · 2025Article
- Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.Journal of psychopharmacology (Oxford, England) · 2024Article
- Pharmaco-EEG analysis of ligands varying in selectivity for α1 subunit-containing GABAPsychopharmacology · 2023Article
- Anxiolytic-Pharmaceuticals (Basel, Switzerland) · 2023Article
- Ablation ofGenes · 2023Article
- Benzodiazepine Modulation of GABABiomolecules · 2022Review
- GABAergic circuits of the basolateral amygdala and generation of anxiety after traumatic brain injury.Amino acids · 2022Review
- GABAFrontiers in psychiatry · 2022Review
- α2-containing γ-aminobutyric acid type A receptors promote stress resiliency in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Zona incerta subpopulations differentially encode and modulate anxiety.Science advances · 2021Article
- Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders.Molecular psychiatry · 2021Review
- Tolerance and dependence following chronic alprazolam treatment: quantitative observation studies in female rhesus monkeys.Psychopharmacology · 2020Article
- Evaluation of the anti-conflict, reinforcing, and sedative effects of YT-III-31, a ligand functionally selective for α3 subunit-containing GABAJournal of psychopharmacology (Oxford, England) · 2020Article
- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.Acta pharmacologica Sinica · 2019Review
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Benzodiazepines have been widely used for their anxiolytic actions. However, the contribution of GABAA receptor subtypes to anxiolysis is still controversial. Studies with mutant mice harboring diazepam-insensitive α-subunits α1, α2, α3, or α5 have revealed that α2-containing GABAA receptors (α2-GABAARs) are required for diazepam-induced anxiolysis, with no evidence for an involvement of any other α-subunit, whereas TP003, described as a selective modulator of α3-containing GABAA receptors, was shown to be anxiolytic. Here, we describe a novel, systematic approach to evaluate the role of positive allosteric modulation of each of the four diazepam-sensitive α-subtypes in anxiety-related behavioral paradigms. By combining H to R point mutations in three out of the four diazepam-sensitive α-subunits in mice with a 129X1/SvJ background, diazepam becomes a subtype-specific modulator of the remaining non-mutated α-subtype. Modulation of α5-GABAARs, but not of α2-GABAARs, increased the time in the light side of the light-dark box as well as open-arm exploration in the elevated plus maze. In contrast, modulation of α3-GABAARs decreased open-arm exploration, whereas modulation of α2-GABAARs increased time in the center in the open-field test. Modulation of any single α-subtype had no effect on stress-induced hyperthermia. Our results provide evidence that modulation of α5-GABAARs elicits anxiolytic-like actions, whereas our data do not provide evidence for an anxiolytic-like action of α3-GABAARs. Thus, α5-GABAARs may be suitable targets for novel anxiolytic drugs.
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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.