Environmental Enrichment alters the behavioral phenotype of a unique animal model of mood disorders

O'Connor AM, Turner CA, Aurbach EL, Hebda-Bauer EK, Watson SJ, Akil H
Society for Neuroscience. 2017.


Selectively bred High-Responder (bHR) and bred Low-Responder (bLR) rats present a novel rodent model of mood disorders. bHR animals emulate externalizing mood disorders such as addiction and impulsivity, and bLR animals emulate internalizing mood disorders such as depression and anxiety. Environmental enrichment (EE) has previously been shown to decrease anxiety-like behavior of adult bLRs and alter social behaviors of adult bHRs. Adolescence is a critical window for the development of emotional centers within the brain, and is a time of increased negative social interactions; by early adolescence, bHR and bLR animals show differential behavioral phenotypes. The effect of EE during adolescence on emotional behavior in these lines has not yet been determined. This study investigates the impact of adolescent EE on anxiety-like behavior of bHR and bLR animals following a social stressor. Male animals from generations F49 and F53 of the colony maintained at the University of Michigan were placed into enriched environments (E) for one hour a day, 5 days a week starting at 35 days postnatal (P35) and ending at P60. Control animals were handled and placed into large cages for the same time period (C) or left in standard housing with no handling (S). Half of all animals underwent social defeat (SD) from P60 until P64. All animals underwent behavioral testing P65 - P67. P65 and P66 testing consisted of a two day social interaction assessment; on day one animals were exposed to an empty open field and on day two a novel animal was present within the open field. Elevated Plus Maze (EPM) testing was carried out on day P67. All animals were sacrificed on P68, brains collected and snap frozen for processing. Exposure to EE decreased anxiety-like behaviors in bHRs, with animals exposed to EE spending more time in the center of the open field (P=0.024) and on the open arms of the EPM (P=0.011). EE prior to SD decreased social anxiety in bLRs, with EE + SD animals showing decreased social avoidance compared to bLR S + SD animals (P=0.028). EE decreased social interaction anxiety in bHRs, regardless of SD status (P=0.020). bLR animals that experienced EE prior to SD showed “bHR-like” patterns of behavior during social interaction testing, with a similar ratio of social interaction/avoidance when a novel animal was present in the open-field. It appears that exposure to EE during adolescence “flips” the bLR phenotype regarding social behavior when animals are subject to SD, suggesting that both genotype and environment influence animals’ response to stressors.