ArticleNature communications2021
Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The genetics of trichotillomania and excoriation disorder: A systematic review.Comprehensive psychiatry · 2024Pooled it
- Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cadherin 11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit.Molecular psychiatry · 2026Article
- Letter to the editor: Comments on 'Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming' by Brownstien et al. (2024).Molecular psychiatry · 2025Article
- Frontostriatal salience network expands as executive networks contract in Obsessive-Compulsive Disorder.bioRxiv : the preprint server for biology · 2025Article
- Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment.The international journal of neuropsychopharmacology · 2025Article
- Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming.Molecular psychiatry · 2025Article
- Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming.bioRxiv : the preprint server for biology · 2024Article
- Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors.Nature neuroscience · 2024Article
- Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.Nature communications · 2024Article
- Informational Analysis and Prediction of Obsessive-Compulsive Disorder Pathogenesis.Psychiatry investigation · 2024Article
- Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model.Nature communications · 2023Article
- Review
- Acute (Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine's therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity reduced compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. Finally, we demonstrate that ketamine blocks the exacerbation of grooming in KO mice caused by optogenetically inhibiting fronto-striatal activity. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine's therapeutic effects in OCD.
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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.