Chronic lithium exposure attenuates ketamine-induced mania-like behavior and c-Fos expression in the forebrain of mice.
Tianhao Gao, Rongjun Ni, Shasha Liu, Yang Tian, Jinxue Wei, Lian-sheng Zhao, Qirun Wang, Peiyan Ni, Xiao-hong Ma, Tao Li
Pharmacology, Biochemistry, and Behavior January 12, 2021 DOI: 10.1016/j.pbb.2021.173108 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Lithium Ketamine |
| Topics | Esketamine Ketamine |
| Key points | Chronic lithium pretreatment attenuates ketamine-induced mania-like behavior and c-Fos expression in specific forebrain regions of mice. |
Abstract
Ketamine, a dissociative anaesthetic, has been used in the treatment of major depressive disorder (MDD) as a rapid acting antidepressant drug. Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in MDD patients. Lithium is a well-known mood stabilizer and has been widely used for the treatment of mania. It is not fully understood which forebrain regions are involved in ketamine- and lithium-induced expression of c-Fos. Therefore, our aim was to investigate the effect of chronic lithium treatment on mania-like behavior and c-Fos expression in the mouse forebrain activated by a single administration of ketamine. In the open field test, our results showed that ketamine significantly increased the total distance and total cumulative duration of movement in mice, while chronic lithium could attenuate these effects of ketamine. In addition, acute ketamine induced higher c-Fos expression in the lateral septal nucleus, hypothalamus, amygdala, and hippocampus of mice in the treatment group compared to those in the control group. However, chronic lithium inhibited the significant increase in c-Fos-immunoreactive neurons following acute ketamine administration in the dentate gyrus of the hippocampus, field CA1 of the hippocampus, dorsal subiculum, ventral subiculum, ventral subiculum, central amygdaloid nucleus and basolateral amygdaloid nucleus. In summary, our research shows that pretreatment with lithium moderates the effects of acute ketamine administration on mania-like behavior and c-Fos expression in the forebrain. These findings could be helpful in better understanding the episodes of mania related to ketamine treatment for MDD and bipolar disorder.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Lithium attenuates ketamine-induced long-term neurotoxicity through DISC1-mediated GSK-3β/β-catenin and ERK/CREB pathways. Toxicology Letters April 1, 2025
- Overlap and Divergence in Ketamine and Lithium Response in Bipolar Disorder: A Scoping Review Pharmaceuticals November 3, 2025
- Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway Zoological Research November 18, 2022
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