RT Journal Article SR Electronic T1 Inner Ear Arginine Vasopressin-Vasopressin Receptor 2-Aquaporin 2 Signaling Pathway Is Involved in the Induction of Motion Sickness JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 248 OP 260 DO 10.1124/jpet.119.264390 VO 373 IS 2 A1 Li-Hua Xu A1 Yao Yang A1 Hong-Xia Liu A1 Shui-Feng Xiao A1 Wen-Xia Qiu A1 Jin-Xing Wang A1 Chen-Chen Zhao A1 Yuan-Hong Gui A1 Gui-Zhu Liu A1 Bin Peng A1 Xia Li A1 Guo-Hua Wang A1 Xin Zhou A1 Zheng-Lin Jiang YR 2020 UL http://jpet.aspetjournals.org/content/373/2/248.abstract AB It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus– or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness.SIGNIFICANCE STATEMENT Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.