Open Access Peer-reviewed Research Article

A novel role of NK3 receptor signaling in bipolar disorder

Main Article Content

Wei Zhang
Linyao Yu
Yaoqin Shi
Yingtian Zhang
Min Xu
Yang Xu
Chunmei Li
Jingwei Tian corresponding author


Objective: Bipolar disorder (BD) affects more than 1% of the global population with limited therapeutic options. The neurokinin B (NKB)-neurokinin B receptor (NK3R) is involved in a variety of emotional activities. This study explored the role of NK3 receptor signaling in bipolar disorder.
Materials and methods: In this study, a model of intracerebroventricular (ICV) administration of OUA-induced BD was used to investigate the possible role of NK3R signaling in BD. The involvement of NK3R in the expression of OUA-induced BD was assessed by genetically knocking down the NK3R-encoding TACR3 gene with shRNA approach in the hippocampus and systemic administration of a NK3R antagonist ESN364,. Biochemical techniques were used to examine the NK3R-associated signaling changes and the oxidative stress parameters in the hippocampus of BD rats.
Results: The NK3R expression level was elevated in the hippocampus BD rats. Both TACR3 knockdown in the hippocampus and ESN364 treatment reversed the manic-like and depression-like behaviors in BD rats Inhibition of the NK3R signaling reversed oxidative stress-induced damage via upregulating the BDNF signaling pathway in the hippocampus.
Conclusion: These results demonstrated that NK3R signaling plays a key role in the pathogenesis of BD and that pharmacological antagonist of NK3R such as ESN364 could represent a novel therapeutic strategy for the management of BD.

bipolar disorder, hippocampus, NK3R, ESN364, oxidative stress

Article Details

Supporting Agencies
This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2020MH411).
How to Cite
Zhang, W., Yu, L., Shi, Y., Zhang, Y., Xu, M., Xu, Y., Li, C., & Tian, J. (2024). A novel role of NK3 receptor signaling in bipolar disorder. Journal of Pharmaceutical and Biopharmaceutical Research, 5(1), 382-395.


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