ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
Impaired instrumental reversal learning is associated with increased medial prefrontal cortex activity in Sapap3 knockout mouse model of compulsive behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- The genetics of trichotillomania and excoriation disorder: A systematic review.Comprehensive psychiatry · 2024Pooled it
- Invasive and Non-invasive Neurostimulation for OCD.Current topics in behavioral neurosciences · 2021Pooled it
- A Gut-Brain Axis Underlying Succinate-Associated Compulsive-Like Behavior.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Psilocybin restores social novelty investigation in male SAPAP3 knockout mice and engages prefrontal-hippocampal circuitry.Molecular psychiatry · 2026Article
- The relationship between duration of access to intravenous oxycodone self-administration, economic demand for oxycodone, and cognition in rats.Psychopharmacology · 2026Article
- Male Sapap3 knockout mice show threat bias under conflict during platform-mediated avoidance task: effects of extinction with response prevention and implications for obsessive compulsive disorder.Translational psychiatry · 2026Article
- Aberrant Medial Prefrontal Cortex Activity and Flexible Behavior in the TgF344-AD Rat Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Daytime lighting conditions alter home-cage behavior across both sexes in diurnal grass rats.Frontiers in neuroscience · 2026Article
- Reward contingency reorganizes lateral orbitofrontal cortex pyramidal neuron activity from reward-aligned to action-aligned during associative learning.Frontiers in cellular neuroscience · 2026Article
- Dorsomedial Striatal Scube1 Expression Correlates With Perseveration in a Rat Reversal-Learning Task.Cureus · 2025Article
- Complementary corticostriatal circuits orchestrate action repetition and switching.Science advances · 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
- Advancing Obsessive-Compulsive Disorder Research: Insights from Transgenic Animal Models and Innovative Therapies.Brain sciences · 2025Review
- Late development of OCD-like phenotypes in Dlgap1 knockout mice.Psychopharmacology · 2025Article
- Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.Neuroscience bulletin · 2024Review
- Striosomes control dopamine via dual pathways paralleling canonical basal ganglia circuits.Current biology : CB · 2024Article
- Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems.bioRxiv : the preprint server for biology · 2024Article
- 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
- Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.Nature communications · 2024Article
- Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model.Nature communications · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Convergent functional neuroimaging findings implicate hyperactivity across the prefrontal cortex (PFC) and striatum in the neuropathology of obsessive compulsive disorder (OCD). The impact of cortico-striatal circuit hyperactivity on executive functions subserved by these circuits is unclear, because impaired recruitment of PFC has also been observed in OCD patients during paradigms assessing cognitive flexibility. To investigate the relationship between cortico-striatal circuit disturbances and cognitive functioning relevant to OCD, Sapap3 knockout mice (KOs) and littermate controls were tested in an instrumental reversal-learning paradigm to assess cognitive flexibility. Cortical and striatal activation associated with reversal learning was assessed via quantitative analysis of expression of the immediate early gene cFos and generalized linear mixed-effects models. Sapap3-KOs displayed heterogeneous reversal-learning performance, with almost half (n = 13/28) failing to acquire the reversed contingency, while the other 15/28 had similar acquisition as controls. Notably, reversal impairments were not correlated with compulsive grooming severity. cFos analysis revealed that reversal performance declined as medial PFC (mPFC) activity increased in Sapap3-KOs. No such relationship was observed in controls. Our studies are among the first to describe cognitive impairments in a transgenic OCD-relevant model, and demonstrate pronounced heterogeneity among Sapap3-KOs. These findings suggest that increased neural activity in mPFC is associated with impaired reversal learning in Sapap3-KOs, providing a likely neural basis for this observed heterogeneity. The Sapap3-KO model is thus a useful tool for future mechanistic studies to determine how mPFC hyperactivity contributes to OCD-relevant cognitive dysfunction.
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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.