Effects of Environmental Enrichment on Repetitive Behaviors in the BTBR T+Tf/J Mouse Model of Autism

Background:  BTBR T+tf/J (BTBR) mice have recently emerged as a well-validated mouse model of autism due to their manifestation of core phenotypic autism behaviors: impaired socialization, deficits in communication and repetitive behaviors. While it is unknown whether BTBR mice share a cause of these altered behaviors with autism in humans, the collective manifestation of these symptoms provides a model in which treatment options may be explored in phenotypic behaviors of interest. Specifically the presence of both lower and higher order repetitive behaviors make the BTBR mouse a promising model for testing the effects of therapeutic interventions for the reduction of repetitive behaviors in autism.

Objectives:  To evaluate the effectiveness of environmental enrichment for reducing repetitive behaviors in the BTBR mice. We hypothesized that housing in an enriched condition would reduce the number of higher and lower order repetitive behaviors seen in this strain.

Methods:  All research was conducted in a laboratory setting at a research university; all procedures were approved by the institutional animal care and use committee.  Subjects were 15 BTBR male mice and 16 control C57BL/6J (B6) male mice; mice from each strain were randomly assigned to either control or enriched housing.  Lower order behaviors were captured by assaying the time and sequence of grooming, while higher order behaviors were measured using a pattern analysis of an object exploration task from digital recordings. Baseline scores were established at 7 weeks of age, followed by 30 days of housing in either standard or enriched cage. Baseline scores were compared between strains at baseline using T-tests; Post-tests scores were analyzed using a two-way analysis of variance which allowed us to examine differences based on strain, housing condition, and the interaction of strain x housing condition.

Results:  As expected, BTBR mice spent significantly more time grooming and had more rigid grooming sequence than control mice at baseline. After 30 days of enrichment housing, BTBR mice demonstrated a significant reduction in time spent grooming, resulting in levels that were lower than those exhibited by BTBR mice in standard housing. No changes were seen in the rigidity of the grooming sequence. In contrast to previous findings, no differences were found for higher order repetitive behaviors between strains at baseline. Subsequently, enrichment did not significantly alter the number of higher order repetitive behaviors at posttest.

Conclusions:  The results suggest that environmental enrichment may be beneficial for reducing the time spent engaging in lower order repetitive behaviors, but may not change the overall quality of the behaviors when they do manifest. Extracting information about human ASD from animal models must be done with caution. That said, our research supports a hypothesis that therapeutically engaging children with ASDs in stimulating sensory-motor activities may be beneficial in reducing some types of repetitive behavior.