Provocative motion elicits hypothermia and tail vasodilation in rats and shrews: A new index of motion sickness in pre-clinical studies?

Cardinal symptoms of motion sickness in humans include cold sweating, nausea and vomiting, and facial pallor; these indices cannot be employed in most laboratory animals. Few human studies also reported motion sickness-related hypothermia due to cutaneous vasodilation in the limbs. The aim of the present study was to investigate whether similar motion-induced hypothermic responses are present in rats and in musk shrews (an insectivore possessing vomiting reflex). Adult male Wistar rats were administered either antiemetic ondansetron (0.5 mg/kg s.c.) or vehicle, and 30 min later were subjected to provocative motion (rotation 0.5 Hz, 40 min) in their home cages; the experiment was repeated one week later using a crossover design (n = 7). Rotation provoked mild hypothermia (from 37.4 ± 0.1 to 35.6 ± 0.2 °C, p < 0.001) that was attenuated by ondansetron by 28% (p < 0.05). In another group of un-instrumented rats, we used infrared thermography and found that rotation induced a transient increase of tail temperature (from 22.9 ± 0.6 to 25.1 ± 0.6 °C, p < 0.05) indicative of vasodilation; this rise preceded the fall in the core body temperature seen in the telemetered studies. Infrared thermography was also used to investigate skin temperature changes induced by motion (linear shaker, 1 Hz, 15 min) in shrews (n = 6). All animals exhibited episodes of retching and/or vomiting (latency 205 ± 38 s) that was preceded by a transient increase in tail temperature (from 24.0 ± 1.5 to 27.0 ± 2.2 °C, p < 0.05). A fall of interscapular temperature (from 38.4 ± 0.5 to 36.6 ± 0.4 °C, p < 0.001) was also seen during motion testing. Provocative motion induces hypothermia via mechanism involving dilatation of the vascular bed of the tail. The tail vasodilation that precedes retching/vomiting in Suncus murinus, and the tail vasodilation in rats could form the basis of a potential index of nausea in experimental animals.