Role of mTOR1 signaling in the antidepressant effects of ketamine and the potential of mTORC1 activators as novel antidepressants.
Taro Kato
Neuropharmacology February 1, 2023 DOI: 10.1016/j.neuropharm.2022.109325 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Antidepressants Glutamatergic signaling Mtorc1 |
| Key findings | The authors argue that mTORC1 signaling and the resulting increase in synapse formation in the medial prefrontal cortex play a key role in ketamine's rapid antidepressant effects, and propose that mTORC1 signaling itself could be a drug discovery target. |
Abstract
Conventional antidepressant medications act on monoaminergic systems and have important limitations, including a therapeutic delay of weeks to months and low rates of efficacy. Recently, clinical findings have indicated that ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate receptor channel activity, causes rapid and long-lasting antidepressant effects. Although the exact mechanisms underlying the antidepressant effects of ketamine are not fully known, preclinical studies have demonstrated a key role for mechanistic target of rapamycin complex 1 (mTORC1) signaling and a subsequent increase in synapse formation in the medial prefrontal cortex. In this review, we discuss the role of mTORC1 and its subsequent signaling cascade in the antidepressant effects of ketamine and other compounds with glutamatergic mechanisms of action. We also present the possibility that mTORC1 signaling itself is a drug discovery target.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |