Molecular and cellular basis of obsessive–compulsive disorder-like behaviors: emerging view from mouse models
Abstract
PURPOSE OF REVIEW: This article reviews recent literature describing novel mouse genetic models of obsessive-compulsive disorder-like behaviors and neurobiological insights gained from analyses of such models. RECENT FINDINGS: Obsessive-compulsive disorder is a common neuropsychiatric disorder characterized by recurrent intrusive thoughts (obsessions) and ritualistic (compulsive) behaviors. Although the cause of this disorder remains unclear, recent studies of novel mouse genetic models with excessive grooming behaviors have begun to shed light on the molecular and cellular mechanisms underlying the pathogenesis of 'obsessive-compulsive disorder-like' behaviors. Genetic deletion of three genes in mice, Hoxb8, Sapap3, and Slitrk5, leads to pathological behaviors including adult-onset excessive grooming with mild-to-severe hair loss and self-injury. In two of the models, the Sapap3-deficient and the Slitrk5-deficient mice, the abnormal grooming behaviors are associated with enhanced anxiety and these pathological behaviors can be curtailed with subchronic administration of a selective serotonin reuptake inhibitor, suggesting the predictive validity of such models. Molecular, pathophysiological, and genetic analyses of these models reveal several insights on the etiological basis of abnormal behaviors in these mice, including abnormal cortico-striatal synapse formation and function in Sapap3 mice, impaired development and function of bone marrow-derived microglia in Hoxb8 mice, and abnormal striatal neuronal differentiation and neurotransmission in Slitrk5 mice. SUMMARY: Novel animal models provide powerful tools to investigate the molecular, cellular, and circuitry mechanisms of obsessive-compulsive disorder-like behaviors. Detailed analyses of these models may provide candidate molecules and mechanisms for the investigation of cause and therapy of obsessive-compulsive disorder.
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In mice, the neural substrate for the stereotyped grooming sequence lies in several brain regions including the brain stem and the striatum, where the striatum is thought to regulate the initiation and modulation of grooming behaviors.
“In mice, the neural substrate for the stereotyped grooming sequence (whisker grooming or coat grooming) lies in several brain regions including the brain stem and the striatum [506], where the striatum is thought to regulate the initiation and modulation of these grooming behaviors [507].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [506]
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- Authors
- Yang, X. W., & Lu, X.-H.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Yang, X William
- Venue
- Current Opinion in Neurology
- Published
- 2011-04
- Volume
- 24
- Issue
- 2
- Pages
- 114-118
- ISSN
- 1350-7540 (ISSN-L)
- OpenAlex
- W2005393669
- Cited by
- 36
- References
- 33
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 10
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (RL1DA024853)
- National Institute of Neurological Disorders and Stroke (PL1NS062410)
- National Center for Research Resources (X02RR023834)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD0995298)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- obsessive-compulsive disorder, genetic mouse models, excessive grooming, Hoxb8, anxiety, corticostriatal synapses, microglia, selective serotonin reuptake inhibitors, hair loss, self-harm
- MeSH terms
- Animals, Behavior, Animal, Compulsive Behavior, Disease Models, Animal, Grooming, Humans, Membrane Proteins, Nerve Tissue Proteins, Obsessive-Compulsive Disorder, Microglia, Homeodomain Proteins, Mice
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