Review
Biochemistry & Molecular Biology
Ji-Woon Kim, Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Summary: Acute administration of (R,S)-ketamine produces rapid and sustained antidepressant effects by blocking NMDA receptors and inducing a novel form of synaptic plasticity in the hippocampus. This triggers downstream signaling events and transcriptional changes that contribute to the antidepressant effects. This review explores the intracellular signaling pathway triggered by ketamine and its connection to synaptic plasticity and sustained antidepressant effects.
TRENDS IN MOLECULAR MEDICINE
(2023)
Review
Neurosciences
Ryota Shinohara, George K. Aghajanian, Chadi G. Abdallah
Summary: The discovery of the rapid-acting antidepressant effects of ketamine has revolutionized our approach to treating severe depression, while also presenting new challenges. It is increasingly crucial to focus on the downstream molecular mechanisms of ketamine and its effects on the brain circuitry and networks.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: This study demonstrates that the loss of GluN2A in adult mouse brains can elicit strong antidepressant-like responses without causing psychomimetic effects similar to Ketamine. The antidepressant effects of Ketamine and MK-801 are mainly mediated by the suppression of GluN2A rather than GluN2B.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: The study found that the loss of GluN2A in adult mice elicits antidepressant-like responses without causing psychomimetic effects similar to ketamine. The antidepressant effects of ketamine and MK-801 are mediated by the suppression of GluN2A, not GluN2B. Additionally, these drugs increase the excitability of hippocampal neurons through GluN2A.
NATURE NEUROSCIENCE
(2023)
Article
Cell Biology
Pei-Yi Lin, Z. Zack Ma, Melissa Mahgoub, Ege T. Kavalali, Lisa M. Monteggia
Summary: Ketamine's rapid antidepressant action is dependent on BDNF-TrkB signaling in CA1 neurons and a specific synaptic locus, suggesting the importance of synaptic potentiation in the hippocampus for its therapeutic effects.
Article
Psychology, Clinical
Anna Feeney, Bettina B. Hoeppner, Marlene P. Freeman, Martina Flynn, Dan V. Iosifescu, Madhukar H. Trivedi, Gerard Sanacora, Sanjay J. Mathew, Charles DeBattista, Dawn F. Ionescu, Cristina Cusin, George I. Papakostas, Manish K. Jha, Maurizio Fava
Summary: This study compares the efficacy of a single infusion of intravenous ketamine and a placebo in treatment-resistant depression patients and finds that concomitant use of oral benzodiazepines may attenuate the antidepressant effects of ketamine.
JOURNAL OF CLINICAL PSYCHIATRY
(2023)
Article
Neurosciences
Dongbin Lyu, Fan Wang, Mengke Zhang, Weichieh Yang, Haijing Huang, Qinte Huang, Chenglin Wu, Nuoshi Qian, Meiti Wang, Huanfei Zhang, Sichai Zheng, Jing Chen, Yingmei Fu, Chen Zhang, Zezhi Li, Wu Hong
Summary: This study found that sub-anesthetic doses of ketamine exert antidepressant effects by inhibiting inflammation and activating autophagy. In addition, ketamine also increased levels of neuroplasticity-related factors and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin.
PSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Yukitoshi Izumi, Fong-Fu Hsu, Charles R. Conway, Peter Nagele, Steven J. Mennerick, Charles F. Zorumski
Summary: Nitrous oxide (N2O) and ketamine have similar hippocampal synaptic enhancement effects and may have therapeutic potential for treatment-resistant major depression.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
Xiao-Hui Tang, Yu-Gang Diao, Zhuo-Yu Ren, Yan-Yu Zang, Guang-Fen Zhang, Xing-Ming Wang, Gui-Fang Duan, Jin-Chun Shen, Kenji Hashimoto, Zhi-Qiang Zhou, Jian-Jun Yang
Summary: Mouse models of depression-like behavior showed decreased levels of GABA and increased levels of glutamate in the hippocampus. Ketamine treatment reversed these alterations by increasing GABA levels and decreasing glutamate levels. These effects were mediated by changes in enzymes and transporters on GABAergic neurons and astrocytes.
Review
Neurosciences
John H. Krystal, Ege T. Kavalali, Lisa M. Monteggia
Summary: Ketamine is a channel blocker that targets NMDA receptors and has shown rapid antidepressant effects, providing a potential new treatment option for mood disorders. This discovery has not only given us a better understanding of the neurobiology of mood disorders, but also shed light on synaptic plasticity mechanisms for its treatment. In this review, we discuss the clinical aspects, synaptic and circuit mechanisms of ketamine, and how these insights can inform future studies for more effective treatments of neuropsychiatric disorders.
NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Psychiatry
Melody J. Y. Kang, Emily Hawken, Gustavo Hector Vazquez
Summary: The mechanism of ketamine's rapid antidepressant effects remains unclear. This study suggests a robust relationship between mood improvements and ketamine-induced increases in molecular neuroplasticity. The findings provide evidence that ketamine may act by restoring deficits in neuroplasticity, particularly involving intracellular signaling molecules.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Neurosciences
Artemis Zavaliangos-Petropulu, Noor B. Al-Sharif, Brandon Taraku, Amber M. Leaver, Ashish K. Sahib, Randall T. Espinoza, Katherine L. Narr
Summary: Major depressive disorder is highly prevalent, but many patients don't respond well to available therapies. Ketamine has shown promise as a treatment, especially for resistant or high-risk patients. Its effects on depression are not fully understood, but neuroimaging studies have revealed changes in brain networks that may contribute to its antidepressant effects. This review summarizes recent research on ketamine's effects on brain structure and function in depressed patients.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2023)
Article
Neurosciences
Xuelong Zhou, Chenjing Zhang, Jiamin Miao, Ziyang Chen, Hongquan Dong, Cunming Liu
Summary: Ketamine exerts rapid antidepressant effects by blocking burst firing in the lateral habenula, but the sustained antidepressant effects may not depend on this mechanism.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Samuel Kohtala
Summary: Ketamine has emerged as an important anesthetic in both human and veterinary medicine over the past 50 years, with recent studies focusing on its rapid antidepressant effects. Efforts to uncover the mechanisms of ketamine in treating depression have been challenging due to its complex dose-dependent effects and unknown neurobiological mechanisms.
PHARMACOLOGICAL REPORTS
(2021)
Review
Neurosciences
Liang Zhou, Jingjing Duan
Summary: Ketamine, a dissociative anesthetic, has rapid and lasting anesthetic effects. Recent studies have also shown its potential as an antidepressant. However, the mechanisms underlying the diverse effects of ketamine and its interaction with NMDA receptors are not fully understood.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)