Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition
Progress in Neuro-psychopharmacology and Biological Psychiatry August 16, 2016 S. Grieco, Yu-yan Cheng, H. Eldar-Finkelman et al.
An antidepressant dose of ketamine (10 mg/kg) increases expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect requiring ketamine-induced inhibition of glycogen synthase kinase-3 (GSK3). A specific GSK3 inhibitor also up-regulates hippocampal IGF2. Administering IGF2 siRNA reduces ketamine's antidepressant effect in the learned helplessness paradigm. Non-depressed resilient mice display higher IGF2 expression than susceptible depressed mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and may confer resilience to depression-like behavior.