Hippocampal PACAP signaling activation triggers a rapid antidepressant response.

Background: The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression, but the underlying cellular and molecular mechanisms remain unclear. Implicated in depression regulation, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is investigated here to examine its role in mediating the rapid antidepressant response.

Methods: The onset of antidepressant response was assessed through depression-related behavioral paradigms.