Monoamine abnormalities in the SAPAP3 knockout model of obsessive-compulsive disorder-related behaviour
Open accessAbstract
Obsessive-compulsive disorder (OCD) is a leading cause of illness-related disability, but the neural mechanisms underlying OCD symptoms are unclear. One potential mechanism of OCD pathology is monoamine dysregulation. Because of the difficulty of studying monoamine signalling in patients, animal models offer a viable alternative to understanding this aspect of OCD pathophysiology. We used HPLC to characterize post-mortem monoamine levels in lateral orbitofrontal cortex (OFC), medial OFC, medial prefrontal cortex and dorsal and ventral striatum of SAPAP-3 knockout (KO) mice, a well-validated model of compulsive-like behaviours in OCD. As predicted from previous studies, excessive grooming was significantly increased in SAPAP-3 KO mice. Overall levels of the serotonin metabolite 5-hydroxyindoleacetic acid (HIAA) and the ratio of 5HIAA/serotonin (serotonin turnover) were increased in all cortical and striatal regions examined. In addition, dihydroxyphenylacetic acid/dopamine ratio was increased in lateral OFC, and HVA/dopamine ratio was increased in lateral and medial OFC. No baseline differences in serotonin or dopamine tissue content were observed. These data provide evidence of monoaminergic dysregulation in a translational model of OCD symptoms and are consistent with aberrant cortical and striatal serotonin and dopamine release/metabolism in SAPAP-3 KO mice. These results are guiding ongoing experiments using circuit and cell-type specific manipulations of dopamine and serotonin to determine the contributions of these monoaminergic systems to compulsive behaviours, and serve here as a touchstone for an expanded discussion of these techniques for precise circuit dissection. This article is part of the discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.
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No alterations in striatal DA concentrations in Sapap3-KO mice have been observed in tissue homogenates.
“Striatal DA levels affect vigor of movements [34], but no alterations in striatal DA concentrations in Sapap3-KO mice have been observed in tissue homogenates [35].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [35]
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Price, J. B., Rusheen, A. E., Barath, A. S., Cabrera, J. M. R., Shin, H., Chang, S.-Y., Kimble, C. J., Bennet, K. E., Blaha, C. D., Lee, K. H., et al. (2020) · Neurosurgical FOCUS · doi:10.3171/2020.4.focus20167 · Cited by 51 · see citing works
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- Authors
- Wood, J., LaPalombara, Z., & Ahmari, S. E.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Ahmari, Susanne E.
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2018-01-29
- Volume
- 373
- Issue
- 1742
- Pages
- 20170023
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC5790822
- OpenAlex
- W2786565991
- Cited by
- 41
- References
- 113
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 2
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH104255, T32MH016804)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- obsessive-compulsive disorder, serotonin, dopamine, serotonin turnover, 5-hydroxyindoleacetic acid, dihydroxyphenylacetic acid, orbitofrontal cortex, striatum, compulsive grooming
- MeSH terms
- Animals, Chromatography, High Pressure Liquid, Disease Models, Animal, Female, Humans, Male, Obsessive-Compulsive Disorder, Serotonin, Biogenic Monoamines, Prefrontal Cortex, Mice, Knockout, Mice, Ventral Striatum
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