Behavioral effects of repeated handling differ in rats reared in social isolation and environmental enrichment

The post-weaning social environment has profound effects on behavior and physiology in rodents. Social isolation increases anxiety-like behaviors and novelty-induced locomotor activity, while environmental enrichment decreases these behaviors. In some cases, the effects of social isolation are ameliorated by repeated handling. The goal of the present study was to determine whether the effects of handling differ in rats reared in social isolation and those reared in an enriched environment. After weaning, male Long-Evans rats were housed individually (ISO)3 or in groups in an enriched environment (EE). During adulthood, rats from each housing condition received four, once-daily, brief handling sessions or remained undisturbed in the home cage. All rats were then tested in the open field, elevated plus maze, and for behavioral responses to d-amphetamine (1.0 mg/kg). EE rats spent more time on the open arms of the elevated plus maze and were more likely than ISO rats to emerge from the start box in the open field, suggesting lower anxiety. Handling significantly decreased open arm time in EE rats and marginally increased open arm time in ISO rats. Housing condition did not affect amphetamine-stimulated locomotor activity, but handling altered the time course of the amphetamine response. ISO rats exhibited significantly fewer stereotyped behaviors than did EE rats, but repeated handling eliminated this difference. These findings support previously published studies that suggest brief handling of adult rats may at least partially ameliorate the effects of post-weaning social isolation on anxiety-like behaviors and psychostimulant sensitivity. Furthermore, there are complex interactions between the effects of housing environment and handling, suggesting that handling may be perceived and/or processed differently, depending on the animal's housing environment.

► Interactions between post-weaning housing environment and handling were examined.
► Social isolation vs. enriched environment, repeated handling vs. no handling.
► Handling increased anxiety in enriched rats, but decreased it in isolated rats.
► Handling increased amphetamine-induced stereotypy only in isolated rats.
► Handling effects are complex and depend on post-weaning housing environment.