Rapid and long-lasting antidepressant-like effects of the pituitary adenylate cyclase-activating polypeptide receptor antagonist PA-915 in chronic stress mouse models.

ABSTRACT: Stress-related disorders, such as depression and anxiety, have been one of the most important medical issues. Accumulating evidence suggests that the activation of the pituitary adenylate cyclase-activating polypeptide and its receptor PAC1 are involved in the stress axis and the development of stress-related disorders. We recently developed PA-915, a small-molecule, non-peptide, high-affinity PAC1 antagonist, and demonstrated that it significantly suppresses anxiety-like behavior in acute stress-induced mice. In this study, we aimed to investigate the behavioral effects of PA-915 in chronic stress-induced mouse models of depression, which included repeated social defeat stress, repeated corticosterone administration, and social isolation rearing. PA-915 ameliorated the increased immobilit

SUBMITTER: Shintani Y 

PROVIDER: S-EPMC12815653 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature