| BACKGROUND:Motion sikeness (MS) is a physiological and pathophysiological disorder induced by various motion stimuli and can results in serious of symptoms and signes including vomiting. MS not only has major influences on traveling activities, but also affects on the special limitary activities, including navigation, flight and space. MS also is a common medical cause of permanent grouding for pilots and student pilots because MS can interfere with their performance in air and flight safety. However, the underlying mechanisms of MS are not well understood and there is not yet a good method to prevent effectively MS. Therefore it is important to study the mechanisms of MS. Some researches imply histaminergic system relates closely to the development of MS. This study aims to investigate on the roles of histamine (HA) and H1 receptors in MS. METHODS:Total of 24 healthy Sprague-Dawley rats were divided randomly into 4 groups,6 rats in each group:Drug(-)/MS(-) control group, in which the rats were not exposed to motion stimuli and not treated with anti-MS drug promethazine before exposure to motion stimuli; Drug(-)/MS(+) group, exposed to motion stimuli but not treated with promethazine; Drug(+)/MS(-) group, treated with promethazine but not exposed to motion stimuli; and Drug(+)/MS(+) group, treated with promethazine for each rat at 30 minutes before exposed to motion stimuli. MS was induced by a complex motion stimuli and the conditioned taste aversion was used as a behavioral indicator of MS in rats. Measuring the intaked volume of 0.15% sodium saccharin solution (SSS) for each rat in 45 minutes after motion stimulus. HA and H1 receptors in the vestibular nucleus of brainstem, vestibular ganglion and utricle of rats were examined by immunofluorescence staining. The expressions of H1 recptor proteins in brainstem and vestibular tissues were detected by western blot. The effects of motion stimulus and anti-MS drug promethazine on the expressions of HA and Hi receptors in the central and peripheral vestibular tissues were evaluated. RESULTS: The mean intaked SSS volume of Drug(-)/MS(+) group was significantly less than that of Drug(-)/MS(-) group (8.8ml vs 15.1ml), p<0.01, which demondtrated MS was induced by this motion stimulus in the rats. The mean intaked SSS volume of Drug(+)/MS(-) group was similar to that of Drug(-)/MS(-) group (14.8ml vs 15.1ml), indicating no significant effect of promethazine on intaking SSS in the rats. The mean intaked SSS volume of Drug(+)/MS(+) group was more than that of Drug(-)/MS(+) group (9.6ml vs 8.8ml, p<0.01) but less than that of Drug(-)/MS(-) group (9.6ml vs 15.1ml, p<0.01) or Drug(+)/MS(-) group (9.6ml vs 14.8ml, p<0.01), which indicated that the inhibited intaking of SSS in MS-induced rats was improved partially by promethazin. Immunofluorescence staining showed the expressions of HA or H1 receptors in the vestibular nucleus of brainstem, vestibular ganglion and utricle of rats and their expressions were enhanced by motion stimuli, but not affected significantly by promethazin. Western blot analysis showed that H1 recptor proteins expressed in the brainstem and vestibular tissues, which also increased after motion stimuli, but the increase was not inhibited by promethazin. CONCLUSION:This complex motion stimulus can induced MS in rat. HA and H1 receptors exist in the structures, including vestibular nucleus of brainstem, vestibular ganglion and utricle, all of them are related closely with the development of MS. Motion stimulus can increase the expressions of HA and H1 receptors in the structures, which are not affected by Anti-MS drug promethazin. This study indicates that histaminergic system is involved in the development of MS. Promethazine, as a blocker of H1 receptor, plays a role of anti-MS by binding H1 receptors rather than by increasing the expression of HA or H1 receptors. |
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