ArticleBiological psychiatry2022
Negative Allosteric Modulation of Gamma-Aminobutyric Acid A Receptors at α5 Subunit-Containing Benzodiazepine Sites Reverses Stress-Induced Anhedonia and Weakened Synaptic Function in Mice.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- Characterizing non-hallucinogenic psychedelics beyond the head twitch response: phenotypic fingerprinting of lisuride and LSD.Translational psychiatry · 2026Article
- αJournal of psychopharmacology (Oxford, England) · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- The NMDA receptor subunit GluN2D is a potential target for rapid antidepressant action.Nature communications · 2025Article
- Sex differences in anhedonia in bipolar depression: a resting-state fMRI study.European archives of psychiatry and clinical neuroscience · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.bioRxiv : the preprint server for biology · 2024Article
- Basmisanil, an α5-GABANeuroscience letters · 2024Article
- Modulators of GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Chemogenetic activation of CRF neurons as a model of chronic stress produces sex-specific physiological and behavioral effects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- The molecular basis of drug selectivity for α5 subunit-containing GABANature structural & molecular biology · 2023Article
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- GABATrends in pharmacological sciences · 2023Review
- Article
- Changes in social, sexual, and hedonic behaviors in rats in response to stress and restoration by a negative allosteric modulator of α5-subunit containing GABA receptor.Behavioural brain research · 2023Article
- Exploring the Molecular Targets for the Antidepressant and Antisuicidal Effects of Ketamine Enantiomers by Using Network Pharmacology and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAbnormal reward processing, typically anhedonia, is a hallmark of human depression and is accompanied by altered functional connectivity in reward circuits. Negative allosteric modulators of GABA
methodsAnhedonia was induced by chronic stress in male mice and assayed by preferences for sucrose and female urine (n = 5-7 mice/group). Hippocampal slices were then prepared for electrophysiological recording (n = 1-6 slices/mouse, 4-6 mice/group). Electroencephalography power was quantified in response to GABA-NAM and ketamine administration (n = 7-9 mice/group).
resultsChronic stress reduced sucrose and female urine preferences and hippocampal temporoammonic-CA1 synaptic strength. A peripheral injection of the GABA-NAM MRK-016 restored hedonic behavior and AMPA-to-NMDA ratios in wild-type mice. These actions were prevented by pretreatment with the benzodiazepine site antagonist flumazenil. MRK-016 administration increased gamma power over the prefrontal cortex in wild-type mice but not α5 knockout mice, whereas ketamine promoted gamma power in both genotypes. Hedonic behavior and AMPA-to-NMDA ratios were only restored by MRK-016 in stressed wild-type mice but not α5 knockout mice.
conclusionsα5-Selective GABA-NAMs exert rapid anti-anhedonic actions and restore the strength of synapses in reward regions by acting at the benzodiazepine site of α5-containing GABA
Indexed as
Identifiers
What 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.