title: Thermoregulatory correlates of nausea in rats and musk shrews.
abstract: Nausea is a prominent symptom and major cause of complaint for patients receiving anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is limited, and their efficacy is questionable. Currently, the development of new compounds with anti-nausea activity is hampered by the lack of physiological correlates of nausea. Physiological correlates are needed because common laboratory rodents lack the vomiting reflex. Furthermore, nausea does not always lead to vomiting. Here, we report the results of studies conducted in four research centers to investigate whether nausea is associated with any specific thermoregulatory symptoms. Two species were studied: the laboratory rat, which has no vomiting reflex, and the house musk shrew (Suncus murinus), which does have a vomiting reflex. In rats, motion sickness was induced by rotating them in their individual cages in the horizontal plane (0.75 Hz, 40 min) and confirmed by reduced food consumption at the onset of dark (active) phase. In 100% of rats tested at three centers, post-rotational sickness was associated with marked (~1.5°C) hypothermia, which was associated with a short-lasting tail-skin vasodilation (skin temperature increased by ~4°C). Pretreatment with ondansetron, a serotonin 5-HT3 receptor antagonist, which is used to treat nausea in patients in chemo- or radiation therapy, attenuated hypothermia by ~30%. In shrews, motion sickness was induced by a cyclical back-and-forth motion (4 cm, 1 Hz, 15 min) and confirmed by the presence of retching and vomiting. In this model, sickness was also accompanied by marked hypothermia (~2°C). Like in rats, the hypothermic response was preceded by transient tail-skin vasodilation. In conclusion, motion sickness is accompanied by hypothermia that involves both autonomic and thermoeffector mechanisms: tail-skin vasodilation and possibly reduction of the interscapular brown adipose tissue activity. These thermoregulatory symptoms may serve as physiological correlates of nausea.
authors.affiliation: Research Center for Neuroscience and Institute of Molecular Bioscience, Mahidol University, Bangkok, Thailand.
authors.forename: Sukonthar
authors.initials: S
authors.lastname: Ngampramuan
authors.forename: Matteo
authors.initials: M
authors.lastname: Cerri
authors.forename: Flavia
authors.initials: F
authors.lastname: Del Vecchio
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Corrigan
authors.forename: Amornrat
authors.initials: A
authors.lastname: Kamphee
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Dragic
authors.forename: John A
authors.initials: JA
authors.lastname: Rudd
authors.forename: Andrej A
authors.initials: AA
authors.lastname: Romanovsky
authors.forename: Eugene
authors.initials: E
authors.lastname: Nalivaiko
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation; D005247:Feeding Behavior; D007035:Hypothermia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D008297:Male; D009041:Motion Sickness / Q000150:complications* / Q000378:metabolism; D009325:Nausea / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry; D012702:Serotonin Antagonists / Q000494:pharmacology; D012788:Shrews; D014664:Vasodilation / Q000187:drug effects; D014839:Vomiting / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C078730:serotonin 5 receptor; D017294:Ondansetron
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