title: Implication of substance P neuronal system in the amygdala as a possible mechanism for hypergravity-induced motion sickness.
abstract: We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.
authors.affiliation: Department of Otolaryngology, Suita Municipal Hospital, Japan. ahorii@ent.med.osaka-u.ac.jp
authors.forename: Arata
authors.initials: A
authors.lastname: Horii
authors.forename: Aya
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Uno
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Takao
authors.initials: T
authors.lastname: Imai
authors.forename: Suetaka
authors.initials: S
authors.lastname: Nishiike
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
mesh_terms: D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018471:Hypergravity / Q000009:adverse effects; D007616:Kaolin / Q000008:administration & dosage; D008297:Male; D009041:Motion Sickness / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D007616:Kaolin