IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine
Translational Psychiatry May 17, 2022 Satoshi Deyama, M. Kondo, Shoichi Shimada et al.
Ketamine's rapid antidepressant effects depend on the sustained release of insulin-like growth factor 1 (IGF-1) in the medial prefrontal cortex (mPFC) of male mice. Blocking IGF-1 in the mPFC before or after ketamine injection prevented its antidepressant-like effects in behavioral tests. IGF-1 acted independently of brain-derived neurotrophic factor (BDNF). Infusing IGF-1 into the mPFC produced antidepressant-like effects even in mice with lipopolysaccharide-induced depression, via activation of mTORC1. The findings indicate that persistent intra-mPFC IGF-1 signaling is essential for ketamine's antidepressant actions.