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Development of a mouse test for repetitive, restricted behaviors: Relevance to autism
Open accessAbstract
Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently demonstrated for one particular olfactory stimulus. Further work is required to determine the characteristics of optimal mouse social stimuli in the olfactory hole-board test.
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“Several naturally occurring inbred strains of mice display behavioral features that recapitulate diagnostic symptoms of neurodevelopmental disorders (59–70).”
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 [65]
In the citing paper
“C58/J (C58) is another commercially available inbred strain of mouse that displays high levels of stereotyped vertical jumping behaviors, relevant to the motor stereotypies of the third diagnostic symptom category of autism (65, 67).”
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 [65]
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Metadata
- Authors
- Moy, S. S., Nadler, J. J., Poe, M. D., Nonneman, R. J., Young, N. B., Koller, B. H., Crawley, J. N., Duncan, G. E., & Bodfish, J. W.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Moy, Sheryl S.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 188
- Issue
- 1
- Pages
- 178-194
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2349090
- OpenAlex
- W2050597016
- Cited by
- 195
- References
- 84
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 13 · 2017: 5 · 2016: 9 · 2015: 14 · 2014: 11 · 2013: 21 · 2012: 26
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5u54mh066418-05)
- National Institute of Mental Health (U54-MH066418, U54 MH 66418, R01MH063398, R21MH085254, R01MH073402, MH063398)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD003110)
- 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 › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- repetitive behavior, autism spectrum disorder, inbred mouse strains, BTBR T+tf/J mice, NMDA receptor hypofunction, GRIN1, resistance to change, restricted interests, self-harm, stereotypy, mouse models of autism
- MeSH terms
- Animals, Autistic Disorder, Behavior, Animal, Carrier Proteins, Discrimination Learning, Disease Models, Animal, Exploratory Behavior, Food Preferences, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Neurologic Mutants, Nerve Tissue Proteins, Set, Psychology, Smell, Social Behavior, Species Specificity, Receptors, N-Methyl-D-Aspartate, Self-Injurious Behavior, Mice
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