title: AVP modulation of the vestibular nucleus via V1b receptors potentially contributes to the development of motion sickness in rat.
abstract: BACKGROUND
  Arginine vasopressin (AVP) is considered to be an etiologic hormone in motion sickness (MS). The present study was designed to investigate whether individual differences in AVP expression in the paraventricular nucleus (PVN) and in modulation on the vestibular nucleus (VN) are involved in MS. Systemic application or microinjection of AVP into rat VN and rotatory stimulus were used to induce conditioned taste aversion (CTA) to 0.15 % saccharin sodium solution as a model of MS.
  
  
  RESULTS
  Intra-VN use of SSR149415, an antagonist of V1b receptors (V1bRs), blunted CTA. AVP inhibited Ca(2+) influxes through L-type Ca(2+) channels and NMDA receptor channels in cultured VN neurones, but antagonised by SSR149415. More AVP and V1bRs were expressed respectively in the PVN and VN after rotatory stimulus, especially in rats susceptible to MS. In the VN, AVP content was low, the AVP mRNA was less expressed, a few AVP-positive fibres were sparsely distributed, and fewer AVP/synaptophysin-positive terminals were identified. Almost no fluoro-ruby-labelled AVP-positive neurones in the PVN were found with retrograde tracing from the VN. SNP analysis of the reported 9 sites of the AVP gene showed significant difference between the groups susceptible and insusceptible to MS at the site rs105235842 in the allele frequencies and genotypes. However, there was not any difference between these two groups in the SNP of the reported 38 sites of V1bR gene.
  
  
  CONCLUSIONS
  AVP, through its modulatory, possibly humoral action on the VN neurones via the mediation of V1bR, may contribute to the development of motion sickness in rats; AVP gene polymorphisms may contribute to the individual difference in the responsive expression of AVP in the PVN; and higher expressions of AVP in the PVN and V1bRs in the VN may contribute to the development of motion sickness in rats after vestibular stimulation.
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. 414279284@qq.com.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Xu
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. 113643792@qq.com.|Present Address: Department of Nursing, Jiangsu Provincial Xuzhou Pharmaceutical Vocational College, Xuzhou, Jiangsu, 221116, China. 113643792@qq.com.
authors.forename: Guan-Rong
authors.initials: GR
authors.lastname: Tang
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. 723192783@qq.com.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. 597397971@qq.com.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. ljch@ntu.edu.cn.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Li
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, China. jiangzl@ntu.edu.cn.
authors.forename: Zheng-Lin
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use; D001127:Arginine Vasopressin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D001370:Axonal Transport; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling; D002478:Cells, Cultured; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D004408:Dysgeusia / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008845:Microinjections; D009041:Motion Sickness / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D009411:Nerve Endings / Q000737:chemistry; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017483:Receptors, Vasopressin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012399:Rotation; D012439:Saccharin; D016708:Synaptophysin / Q000032:analysis; D014726:Vestibular Nuclei / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D020746:Calcium Channels, L-Type; D007211:Indoles; D011759:Pyrrolidines; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017483:Receptors, Vasopressin; D016708:Synaptophysin; C569016:Syp protein, rat; D001127:Arginine Vasopressin; D012439:Saccharin