Abstract
Lithium is a common medication used to treat mania and bipolar disorder, but the mechanisms by which lithium stabilizes mood and modifies aggression are still not fully understood. Here we found that acute but not chronic lithium significantly suppresses aggression without affecting locomotion in Drosophila melanogaster. Male flies treated with acute lithium are also less competitive than control males in establishing dominance. We also provided evidence that glycogen synthase kinase-3 (GSK-3), a well-known target of lithium, plays an important role in the anti-aggressive effect of lithium in Drosophila. Our genetic data showed that acute knockdown of GSK-3 in neurons can mimic the inhibitory effect of acute lithium on aggression, while specific overexpression of GSK-3 in a subset of P1 neurons profoundly promotes aggression which can be partially rescued by acute lithium application. Thus, these findings revealed the inhibitory effect of lithium on aggression in Drosophila and laid a groundwork for using Drosophila as a powerful model to investigate the mechanisms by which lithium reduces aggression.
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Acknowledgements
We thank Dr. Xianhui Wang (Chinese Academy of Sciences) and Dr. Yingxue Wang (Max Planck Florida Institute for Neuroscience) for their comments on the manuscript. We also thank Dr. Yufeng Pan (Southeast University) for his valuable comments on the revised manuscript. We thank the members of Zhou lab for their helpful discussion and their support on this study.
Funding
This research was supported by the Strategic Priority Research Program of the Chinese Academy of Science (No. XDB11010800) and National Natural Science Foundation of China (No. 31872280, 31622054). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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RW designed and performed the experiments. BM analyzed the majority of the data. KS analyzed the data from locomotion assays. RW and BM wrote the original draft. FW revised the article. CZ conceived and supervised the project.
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Wang, R., Ma, B., Shi, K. et al. Effects of lithium on aggression in Drosophila. Neuropsychopharmacol. 48, 754–763 (2023). https://doi.org/10.1038/s41386-022-01475-2
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DOI: https://doi.org/10.1038/s41386-022-01475-2
