Corticosterone regulates the balance between freezing and rearing in defensive responses to predator threat

The hormonal stress response critically shapes how animals respond to threats. We examined how corticosterone (CORT) synthesis modulates defensive behaviors in mice exposed to the synthetic predator odor 2,4,5-trimethylthiazoline (TMT). Pharmacological inhibition of CORT synthesis using metyrapone reduced freezing and increased rearing during TMT exposure, without impairing threat recognition-evidenced by robust conditioned place aversion and context-specific freezing. We also found that freezing increased upon repeated TMT exposure, but this effect was blunted when CORT synthesis was blocked during the initial encounter. Furthermore, stress priming via restraint or footshock replicated the effects of prior TMT exposure, enhancing freezing and suppressing rearing. These findings suggest that while recognition of TMT's aversiveness remains intact without CORT, this hormone is essential for determining the qualitative and temporal dynamics of defensive responses. Our results reveal a key role for CORT in shaping behavioral flexibility during threat perception.