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Characterization of behavioral phenotypes in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorder under social housing conditions using the multiple animal positioning system.

ABSTRACT: The BTBR T+ Itpr3tf/J (BTBR) mouse strain is a widely used model of autism spectrum disorder (ASD). The BTBR mice display behavior consistent with the three diagnostic categories of ASD. However, the behavioral phenotypes of the BTBR mice in a long-term group housing setting are largely unknown because conventional behavioral tests for ASD model mice are designed for use under simplified artificial conditions over a short observation period. In this study, we applied a newly developed assay system, the Multiple Animal Positioning System (MAPS), to quantify behaviors under group housing conditions over four days of continuous observation. Using MAPS, we showed that in a group housing condition, the BTBR mice exhibited lower activity levels in the dark phase and alteration of social behavior in comparison with the C57BL/6J mice. The phenotypes of the BTBR mice were affected by co-housing with the C57BL/6J mice for four days, but the influence was weak and limited. Our results by MAPS differ from those obtained using conventional behavioral tests. The present study demonstrated that MAPS would be useful for evaluating the usual/natural behaviors of various animal models in detail and under more ethological conditions.

SUBMITTER: Endo N

PROVIDER: S-EPMC6699967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Autism is a neurodevelopmental disorder in which the first diagnostic symptom is unusual reciprocal social interactions. Approximately half of the children diagnosed with an autism spectrum disorder also have intellectual impairments. General cognitive abilities may be fundamental to many aspects of social cognition. Cognitive enhancers could conceivably be of significant benefit to children and adults with autism. AMPAKINE compounds are a novel class of pharmacological agents that act as positive modulators of AMPA receptors to enhance excitatory glutamatergic neurotransmission. This class of compounds was reported to improve learning and memory in several rodent and non-human primate tasks, and to normalize respiratory abnormalities in a mouse model of Rett syndrome. Here we evaluate the actions of AMPA compounds in adult male and female BTBR mice, a well characterized mouse model of autism. Acute treatment with CX1837 and CX1739 reversed the deficit in sociability in BTBR mice on the most sensitive parameter, time spent sniffing a novel mouse as compared to time spent sniffing a novel object. The less sensitive parameter, time in the chamber containing the novel mouse versus time in the chamber containing the novel object, was not rescued by CX1837 or CX1739 treatment. Preliminary data with CX546, in which β-cyclodextrin was the vehicle, revealed behavioral effects of the acute intraperitoneal and oral administration of vehicle alone. To circumvent the artifacts introduced by the vehicle administration, we employed a novel treatment regimen using pellets of peanut butter for drug delivery. Absence of vehicle treatment effects when CX1837 and CX1739 were given in the peanut butter pellets, to multiple cohorts of BTBR and B6 control mice, confirmed that the pharmacologically-induced improvements in sociability in BTBR were not confounded by the administration procedures. The highest dose of CX1837 improved the cognitive deficit in novel object recognition in BTBR. No drug effects were detected on the high levels of repetitive self-grooming in BTBR. In open field tests, CX1837 and CX1739 did not induce hyperactivity or sedation in either strain. It is interesting to speculate that the ability of CX1837 and CX1739 to restore aspects of sociability in BTBR mice could utilize synaptic mechanisms regulating social cognition, suggesting a potential pharmacological target for interventions to treat symptoms of autism. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Dataset Information

Characterization of behavioral phenotypes in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorder under social housing conditions using the multiple animal positioning system.

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