Low-dose ketamine improves LPS-induced depression-like behavior in rats by activating cholinergic anti-inflammatory pathways.
Jinghua Zhao, XueJie Liu, Daiyue Chang, Xintong Zhang, Huimin Lian, Xueman Du, Li Gao
ACS Chemical Neuroscience February 3, 2020 DOI: 10.1021/acschemneuro.9b00669 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study with in vitro experiments Peer reviewed |
|---|---|
| Population | Rats and PC12 nerve cells |
| Interventions | Ketamine GTS-21 methyllycaconatine α7nAChR-siRNA |
| Topics | Depression Esketamine Ketamine |
| Key findings | Low-dose ketamine produces rapid antidepressant effects by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway. |
Abstract
About 16% of the world's population has major depressive disorder. Traditional antidepressants have slow effect rates and low response rates. Many studies have shown that low doses of ketamine can produce rapid and effective antidepressant effects. However, its mechanism of action needs further exploration. Lipopolysaccharide (LPS) was used to establish a depression model in rats and PC12 nerve cells were used for in vitro experiments. (2,4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a specific agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), was used to compare the rapid antidepressant effect of ketamine. Different doses of α7nAChR antagonist methyllycaconatine (MLA) and α7nAChR-siRNA were used to interfere with the protective effects of ketamine on neuroinflammation in rats and PC12 cells, respectively. MLA intervention downregulated the anti-inflammatory effects of ketamine and decreased the effects of ketamine on behavior, synaptic plasticity, and Nissl bodies in the neuronal cells. Moreover, the dose of MLA was positively correlated with the inhibitory effect in rat hippocampi and the protective effects of GTS-21 were consistent with ketamine. These results demonstrated that low-dose ketamine could produce neuroprotective effects by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway (CAP) in depression, resulting in a rapid antidepressant effect.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 7
- Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review Journal of Psychopharmacology June 26, 2021
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments Brain, Behavior, & Immunity - Health November 7, 2022
- Discovery of a Novel Orally Active Ketamine Derivative with Dual Analgesic and Antidepressant Activities, Lacking Psychomimetic Effects. ACS Chemical Neuroscience March 5, 2025
- Unveiling the role of single versus repeated low-dose ketamine in attenuating doxorubicin-induced chemobrain and depression in rats: differential modulation of neuroinflammation, phosphorylated GLT-1, SERT, DAT, and BDNF/TrkB signaling. Neuropharmacology June 1, 2026
and 2 more in the library
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
- BDNF — a key transducer of antidepressant effects Neuropharmacology November 11, 2015
and 2 more in the library