| Backgrounds and Objectives:Motion sickness arises when the brain receives conflicting signals from sensoryorgans about the body’s orientation. It can be provoked by abrupt changes in movement,such as those occurring during bumpy rides, turbulent flights, and rough seas. Symptomsof motion sickness include a heaving stomach, sweaty palms, and unrelenting nausea.Apathy, general discomfort, headache, pallor and prostration also occur over a varyingperiod of time, depending on personal susceptibility, the severity and duration of rotationstimulus. If not treated in time or properly, it can cause dehydration or even shock. Motionsickness can occur at any age, a higher incidence of this disease with a geneticpredisposition, but its exact pathogenesis is still unclear. In our preliminary study, it wasfound that, although lack of a vomiting reaction, the rats presented several symptomsinduced by rotation such as piloerection, tremble, urinal and fecal incontinence. All thesesymptoms as well as vomiting reaction are the manifestation of the disorder of autonomicnervous system in motion sickness. Therefore, these symptoms may theoretically be takenas the parameters for motion sickness in rodents replacement of vomiting. A completeevaluation criteria of motion sickness is the most important issue of current motionsickness research. Our previous study have showed that the fecal and urinalincontinence-based evaluation criteria was used to estimate mice and rats’ motion sicknesslevel induced by horizontal rotation. However, whether this fecal and urinalincontinence-based evaluation criteria is suitable to assay the summation, variability andhabituation said to be characteristics of motion sickness is not clear. Whether it is effectiveand sensitive to screen of new anti-motion sickness drugs is to be further confirmed.Therefore, this study was to investigate motion sickness level in mice treated with differentpatterns and time of rotation, habituation, bilateral labyrinthectomy, anti-motion sickness drugs to verified the evaluation criteria of motion sickness, and provide the experimentalbasis to screen of new anti-motion sickness drugs.Methods:This issue through the following experiments verified the evaluation criteria ofmotion sickness and screened of new anti-motion sickness drugs.1. Motion sickness index in mice with different kinds of rotationThere are two kinds of rotation: single-axis rotation and dual-axis rotation. The twokinds of rotation were compared under the same condition for40min on motion sicknessindex. Single-axis rotation, horizontal circular motion around the vertical axis which isperpendicular to the Earth’s surface, the speed was360°/s; dual-axis rotation, in addition toaround the vertical axis, it scroll up and down around the horizontal axis. The peak speedwas360°/s and angular acceleration was20°/s2. During a cycle in dual-axis rotation,(clockwise) rotational velocity was employed with increments from0°/s to peak speed(360°/s) and then from peak speed (360°/s) to0°/s in steps of angular acceleration ordeceleration, and then counter-clockwise, repeat the above process, and so on, until40min.2. Motion sickness index in mice with different patterns of rotationThere were five groups of different patterns according to the experimental devicesetting. Peak speed was60°/s, angular acceleration was80°/s2; peak speed was120°/s,angular acceleration was60°/s2; peak speed was180°/s, angular acceleration was60°/s2;peak speed was240°/s, angular acceleration was40°/s2; peak speed was360°/s, angularacceleration was20°/s2. All of the animals were all subjected to rotary stimulation for40min.3. Motion sickness index in mice with different time of rotationAccording to previous experimental results, we selected the pattern of240°/s peakspeed and40°/s2angular acceleration to stimulate the animals for10min,20min,40minand60min. It started rotation clockwise with40°/s2and after6s while it was the maximum centrifugal (240°/s), it decelerated rotation clockwise with40°/s2, when thespeed was0°/s, it become rotation anticlockwise with40°/s2, and then counter-clockwise,repeat the above process, this process lasted12s, and so the cycle. Under the conditions offour groups of different rotation time, we investigated the influence to motion sicknessindex.4. Motion sickness index after habituation14mice daily at14:00were given rotation (peak speed240°/s and angularacceleration40°/s2) for40min in15days.5. Motion sickness index after bilateral labyrinthectomyWe selected chemical method to destruct the labyrinth. The control group wasintratympanic physiological saline (0.9%NaCl) and the treatment group was intratympanicgentamicin.6. Motion sickness index in mice treated with anti-motion sickness drugsThere are four categories of anti-motion sickness drugs applied in common:anticholinergic drugs, sympathetic drugs, antihistamines and calcium channel blockers. Weselected one of the representatives of them as scopolamine, methylphenidate,diphenhydramine, and nimodipine. We compared the efficacy of them by intraperitonealinjection.7. The application of motion sickness evaluation criteriaWe screened several potentially effective drugs from seven anti-motion sicknessdrugs. Combined with spontaneous activity experiment and climbing pole experiment, thepharmacological effects of these drugs were further evaluated. Application of motionsickness evaluation, scopine efficacy was evaluated after intraperitoneal injection andintracerebroventricular administration.Results:1. Compared with the mice stimulated by single axis rotation, the motion sicknessindex in mice was higher after dual axis rotation. 2. Compared with the other groups, the motion sickness index, with240°/s peakspeed and40°/s2angular acceleration, was the highest of the five groups.3. Compared with the other groups, the motion sickness index was higher afterrotation for40min than any other time with the same rotation pattern.4. The motion sickness index initially increased and then gradually decreased afterrotation for40min for11～15days.5. After bilateral labyrinthectomy, the motion sickness index decreased in micecompared with before treatment.6. After taking anti-motion sickness drugs, the motion sickness index decreased inmice compared with before treatment.7. Sdfky5and sdfky6were selected from seven anti-motion sickness drugs dependon the motion sickness index.8. Combined with spontaneous activity experiment and climbing pole experiment,the pharmacological effects of sdfky5and sdfky6were further evaluated. We found thatthe spontaneous activity experiment was not sensitive and accurate enough. Comparedwith scopolamine, the time of climbing pole was increased, sdfky6was longer than sdfky5,but there was no significant difference between these two drugs.9. Compared with control group, there was no significant difference between the twoconfigurations of sdfky6in motion sickness index, but sdfky6-down was less than anotherin the inhibition of central nervous system.10. Compared with control group, after the intraperitoneal administration, motionsickness index of scopine group did not change significantly; after intracerebroventricularadministration, motion sickness index did not change significantly compared with controlgroup.Conclusion:1. The present work demonstrated that the fecal and urinal incontinence-basedevaluation criteria was suited to evaluating the severity of motion sickness after rotational stimulation.2. Combined with climbing pole experiment, we screened two potentially effectivedrugs from seven new anti-motion sickness drugs. Sdfky6-down was effective to motionsickness and did not lead to drowsiness. Scopine may have no effect on motion sickness.3. Motion sickness index can be used for evaluate the effects of new anti-motionsickness drugs. |
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