Cited by 127Obsessive-Compulsive Spectrum DisordersNeurotransmitter Receptor Influence on BehaviorGenetics and Neurodevelopmental Disorders

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

Katayama, K, Yamada, K, Ornthanalai, V G, Inoue, T, Ota, M, Murphy, N P, Aruga, J·2010·Molecular Psychiatry

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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Crossref · 10.1038/mp.2008.97

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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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