ArticleThe Journal of clinical investigation2016
GABA interneurons mediate the rapid antidepressant-like effects of scopolamine.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 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
84 citing papers in PubMed, 144 citations in OpenAlex.
- Group-Based Symptom Trajectory of Intramuscular Administration of Scopolamine Augmentation in Moderate to Severe Major Depressive Disorder: A Post-Hoc Analysis.Neuropsychiatric disease and treatment · 2023Trial
- Fabrication and efficacy evaluation of scopolamine-loaded dissolving microneedle for rapid antidepressant therapy.International journal of pharmaceutics: X · 2026Article
- Natural Products as GPCR-Targeting Antidepressant Candidates: Advances and Opportunities.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Exploring the Evolving Role of Scopolamine in Pharmacotherapy: From Cognitive Impairment to Neuroplasticity?-A Narrative Review.Molecules (Basel, Switzerland) · 2026Review
- Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Semaphorin 3A-mediated perineuronal nets formation incubates depressive-like behaviors in male mice via activating parvalbumin-expressing interneurons.Molecular psychiatry · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- Article
- 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
- Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Evidence for the Contribution of the miR-206/BDNF Pathway in the Pathophysiology of Depression.The international journal of neuropsychopharmacology · 2024Review
- 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
- Acetylcholine muscarinic M1 receptors in the rodent prefrontal cortex modulate cognitive abilities to establish social hierarchy.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.Brain and behavior · 2024Article
- Depression and the Glutamate/GABA-Glutamine Cycle.Current neuropharmacology · 2024Review
- Evolutionary conservation of putative suicidality-related risk genes that produce diminished motivation corrected by clozapine, lithium and antidepressants.Frontiers in psychiatry · 2024Article
- Growth Hormone Action in Somatostatin Neurons Regulates Anxiety and Fear Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches.Journal of neurochemistry · 2023Review
- Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP.International journal of molecular sciences · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67+) interneurons and glutamatergic (CaMKII+) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies.
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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.