Rapamycin Exerts an Antidepressant Effect and Enhances Myelination in the Prefrontal Cortex of Chronic Restraint Stress Mice.

Depressive disorder is a psychiatric condition that is characterized by the core symptoms of anhedonia and learned helplessness. Myelination loss was recently found in the prefrontal cortex (PFC) of patients with depression and animal models, but the mechanism of this loss is unclear. In our previous study, chronic restraint stress (CRS) mice showed depressive-like symptoms. In this study, we found that myelin was reduced in the PFC of CRS mice. We also observed increased mammalian target of rapamycin (mTOR) phosphorylation levels in the PFC. Chronic injections of rapamycin, a mTOR complex inhibitor, prevented depressive behavior as shown by the forced swimming test and sucrose preference test. Rapamycin also increased myelination in the PFC of CRS mice. In summary, we found that CRS enhanced mTOR signaling and reduced myelination in the PFC and that rapamycin could prevent it. Our study provides the etiology of reduced myelin in depressive symptoms and suggests that mTOR signaling could be a target for treating depression or improving myelination deficits in depressive disorders.