Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities
Abstract
Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.
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Administration of clonidine attenuated the anxiety-like behavior of SLITRK1-deficient mice, providing predictive validity in this TS mouse model.
“Administration of clonidine, an α2-adrenergic receptor agonist often used to treat patients with TS, attenuated the anxiety-like behavior of SLITRK 1-deficient mice, providing predictive validity in this TS mouse model.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [615]
SLITRK1 knockout mice exhibit increased anxiety-like behavior in the elevated plus-maze test and increased levels of norepinephrine and its metabolite in the prefrontal cortex and NAc, but DA levels were not altered.
“SLITRK1 knockout mice exhibit increased anxiety-like behavior in the elevated plus-maze test and neurochemical analyses identified increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol in the prefrontal cortex and NAc, but DA levels were not altered [615].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [615]
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- Authors
- Katayama, K., Yamada, K., Ornthanalai, V. G., Inoue, T., Ota, M., Murphy, N. P., & Aruga, J.
- Affiliations
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Aruga, J
- Venue
- Molecular Psychiatry
- Published
- 2008-09-16
- Volume
- 15
- Issue
- 2
- Pages
- 177-184
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1979361034
- Cited by
- 127
- References
- 39
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 1 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 12 · 2015: 12 · 2014: 13 · 2013: 12 · 2012: 10
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- SLITRK1, anxiety-like behavior, noradrenergic system, norepinephrine, MHPG, clonidine, alpha-2 adrenergic agonists, Tourette syndrome, trichotillomania, elevated plus maze, forced swim test, tail suspension test, depression-like behavior
- MeSH terms
- Adrenergic alpha-Agonists, Animals, Anxiety, Behavior, Animal, Brain, Chromatography, High Pressure Liquid, Clonidine, Conditioning, Classical, Disease Models, Animal, Electrochemistry, Exploratory Behavior, Fear, Membrane Proteins, Nerve Tissue Proteins, Norepinephrine, Swimming, Mice, Knockout, Statistics, Nonparametric, Maze Learning, Hindlimb Suspension, Mice
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