Restraint stress activates defensive behaviors in male rats depending on age and housing condition

Restraint is a widely used experimental stress manipulation in animal models. It is still unclear, however, whether restraint is associated with physical fatigue leading to overall behavioral inhibition, or if it induces activation of defensive behaviors and strategies to protect against subsequent challenges. The aim of this study was to systematically investigate restraint effects in rats based on housing condition (isolation- vs. pair-housed) and age at the time of testing, both of which are relevant to the expression of defensive strategies. Restraint induced behavioral inhibition in male rats younger than postnatal day 65 in an open-field paradigm, while it activated defensive behaviors in adult rats, depending on their housing condition; thereby pair-housed adult rats exhibited a heightened stretch-attend postures (SAPs) and it was suppressed by restraint, while isolation-housed adult rats displayed lower SAPs but it was enhanced by restraint. Restraint also enhanced pain tolerance, but not pain sensitivity, across all ages, regardless of housing conditions. These results suggest that restraint stress activates defensive systems of male rats, including sensory defenses and exploratory strategies in a novel environment, and these expression patterns vary with age from overall inhibition to changes in defensive behavior strategies. Understanding differential changes in these models could lead to greater consistency and better standardization of rodent models commonly used to assess the impact of stress on anxiety and defensive behaviors.