Cited by 195Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

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Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

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Moy, Sheryl S., Nadler, Jessica J., Poe, Michele D., Nonneman, Randal J., Young, Nancy B., Koller, Beverly H., Crawley, Jacqueline N., Duncan, Gary E., Bodfish, James W.·2008·Behavioural Brain Research

DOI 10.1016/j.bbr.2007.10.029PMC PMC2349090

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Abstract

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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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.
ORCID: Moy, Sheryl S.
Koller, Beverly H.
Crawley, Jacqueline N.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2008-03
Volume: 188
Issue: 1
Pages: 178-194
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2007.10.029
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

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