Abstract
The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26–56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors [1]
As ASD occurs in the 4:1 male to female ratio, the current study focused on establishing a behavioral battery for male juvenile rats
The potential to explore genetic, environmental and pharmacological manipulations in a species that exhibits a complex social repertoire makes the laboratory rat an attractive model for preclinical ASD research
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors [1]. Given the prevalence and societal impact of ASD, there is an urgent need for preclinical research to evaluate potential causes, determine the underlying neurobiology and discover novel therapeutic interventions [2]. The majority of ASD preclinical research has been carried out in mouse models that utilize standardized behavioral phenotyping tools to measure ASD-relevant deficits in social behavior, screen for repetitive behaviors and restricted interests, and evaluate associated symptoms, such as anxiety [7]. Standardized approaches have led to more coordinated preclinical research efforts, there remains a need to develop additional behavioral tests that capture the full spectrum of social deficits relevant to ASD [8]. We explore the use of the laboratory rat (Rattus norvegicus) as a model system that can be used to improve translational potential of ASD preclinical research efforts [9]
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