Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP
Open accessAbstract
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two suggested treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums, and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR after treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism.
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Inbred strains are genetically homogeneous and commercially available, maximizing their feasibility as translational tools in medications development.
“These inbred strains are genetically homogeneous and commercially available, maximizing their feasibility as translational tools in medications development (71–73).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [72]
BTBR T+tf/J mice display behavioral phenotypes relevant to all three diagnostic symptoms of autism.
“BTBR T+tf/J (BTBR) is a commercially available inbred strain of mouse that displays behavioral phenotypes relevant to all three diagnostic symptoms of autism (60–62, 64, 66, 68–70, 72, 74–78).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [72]
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Behavioural phenotyping assays for mouse models of autism
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“Mice were scored for spontaneous self-grooming behaviors as described previously (Yang et al., 2007, 2009; McFarlane et al., 2008; Silverman et al., 2010).”
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- Authors
- Silverman, J. L., Tolu, S. S., Barkan, C. L., & Crawley, J. N.
- Affiliations
- National Institute of Mental Health (US)
- Corresponding author
- Silverman, Jill L
- Venue
- Neuropsychopharmacology
- Published
- 2009-12-23
- Volume
- 35
- Issue
- 4
- Pages
- 976-989
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2827881
- OpenAlex
- W2082109123
- Cited by
- 438
- References
- 109
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 17 · 2023: 26 · 2022: 33 · 2021: 23 · 2020: 23 · 2019: 26 · 2018: 24 · 2017: 33 · 2016: 24 · 2015: 24 · 2014: 39 · 2013: 22 · 2012: 38
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, BTBR mice, mGluR5 antagonist, MPEP, risperidone, sociability, repetitive behavior, metabotropic glutamate receptors, sedation
- MeSH terms
- Animals, Autistic Disorder, Disease Models, Animal, Dose-Response Relationship, Drug, Exploratory Behavior, Grooming, Interpersonal Relations, Mice, Inbred C57BL, Mice, Inbred Strains, Pyridines, Stereotyped Behavior, Receptors, Metabotropic Glutamate, Excitatory Amino Acid Antagonists, Statistics, Nonparametric, Mice, Receptor, Metabotropic Glutamate 5
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