Sitagliptin as a therapeutic approach for social anxiety disorder: the role of DPP4 and NPY in modulating social fear and comorbid depressive-like behavior in mice.

ABSTRACT: We have previously shown that neuropeptide Y (NPY) reduces social fear in an animal model that closely mimics the key behavioral symptoms of social anxiety disorder (SAD). Since NPY cannot yet be routinely administered to patients, we investigated the effects of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor approved for the treatment of type 2 diabetes mellitus, on social fear and comorbid depression in mice. In addition to its well-known effects on glucose metabolism, sitagliptin also prevents the degradation of NPY, thereby increasing its concentration in the blood and the brain. We show that sitagliptin administration via drinking water (50 and 100 mg/kg/day, for 4 weeks) not only reduced social fear but also prevented the onset of comorbid depressive-like behavior in outbred C

SUBMITTER: Zoicas I 

PROVIDER: S-EPMC12436601 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature