Medial orbitofrontal cortex activation reduces discrimination for threat in male rats

Recognizing threats is crucial for animals to adopt appropriate behaviors. The orbitofrontal cortex (OFC) is essential for emotional regulation and cognitive flexibility. This study investigated the effect of medial OFC (mOFC) manipulation on discrimination ability in male rats in a fear differential conditioning paradigm. The rats were conditioned to two different types of conditioned stimuli (CS⁺ and CS^-); the CS⁺ was paired with an electric footshock to increase its threat significance, whereas the CS^- was made to be less threatening by not pairing with a footshock. The mOFC was manipulated during either the acquisition or retrieval stage. Inactivation of the mOFC during either stage did not significantly change the differential fear responses to CS⁺ and CS^- or the fear discrimination index. However, mOFC activation during both the acquisition and retrieval stages of the fear differential conditioning paradigm reduced the fear discrimination index by enhancing fear expression to the less threatening signal. These results suggest that mOFC activation impairs the discrimination of environmental information and plays a critical role in modulating fear responses. This research provides insights into the neural mechanisms involved in cognitive flexibility and emotional regulation by clarifying the role of the mOFC in fear discrimination.