Research progress of the mTOR signaling pathway underlying the antidepressant actions of ketamine / 中国药学杂志

ABSTRACT

Depression is a common, serious psychiatric disease. Despite a wide range of antidepressants available, only one third of the patients show significant mood improvement in response lo an initial antidepressant treatment. Moreover, there is a time-lag of weeks to months with currently available medications; the suffering of patients could not be relieved quickly. Ketamine was found to produce rapid antidepressant responses in treatment resistant major depressive disorder patients. Molecular and cellular studies in rodent models demonstrated that ketamine stimulates mammalian target of rapamycin (mTOR) signaling and increases the initial translation of mTOR and downstream molecules, these effects of ketamine are accompanied by increasing levels of maturity and quantity of spine synapses in the prefrontal cortex. Ketamine was found to produce rapid antidepressant responses in treatment of depression. These studies identify the characterization of the mTOR signaling pathway in depression and its action in response to antidepressants shows great potential for the identification of new therapeutic targets for the development of antidepressant drugs.