Contributions of Prelimbic Cortex, Dorsal and Ventral Hippocampus, and Basolateral Amygdala to Fear Return Induced by Elevated Platform Stressor in Rats.

Abstract Fear relapse is a major challenge in the treatment of stress-related mental disorders. Most investigations have focused on fear return induced by stimuli associated with the initial fear learning, while little attention has been paid to fear return evoked after exposure to an unconditioned stressor. This study explored the neural mechanisms of fear return induced by elevated platform (EP) stressor in Sprague-Dawley rats initially subjected to auditory fear conditioning. The contributions of the prelimbic cortex (PL), dorsal hippocampus (DH), ventral hippocampus (VH), and basolateral amygdala (BLA) were examined by targeted bilateral intracerebral injection of the GABAA agonist muscimol after elevated platform (EP) stressor. Muscimol-induced inactivation of PL or BLA significantly impaired the return of conditioning fear, while inactivation of the DH or VH had no effect. These results suggest that fear return induced by non-associative stressor may depend on the PL and BLA but not on the hippocampus.