Role of Histamine H1 Receptors in Vestibular Nucleus in Motion Sickness

ObjectivesTo investigate the expression of histamine H1 receptors (H1R) in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness (MS).MethodsA total of 24 healthy Sprague–Dawley rats were divided randomly into four groups (n=6 each) which determined if the animals would receive induction of MS or drug (promethazine) treatment: MS(–)/Drug(–); MS(+)/Drug(–); MS(–)/Drug(+ at 0.25 mg); and MS(+)/Drug(+). MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution (SS) intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H1R protein in brainstem tissue at vestibular nucleus level was detected by western blot.ResultsThe mean SS intake volume in the MS(+)/Drug(–) group (8.8 ml) was significantly less than that of the MS (–)/Drug(–) group (15.1 ml) (P < 0.01). The mean SS intake volume of the MS(–)/Drug(+) group (14.8 ml) was similar to that of the MS(–)/Drug(–) group. The mean SS intake volume (9.6 ml) of the MS(+)/Drug(+) group was more than that of the MS (+)/Drug(–) group (P < 0.01), but less than that of the MS (–)/Drug(–) group or MS (–)/Drug(+) group (P < 0.01). Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS–induced increase of H1R was not affected significantly by promethazine.ConclusionsH1Rs exist in the vestibular nucleus in rats and H1R expression is up–regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti–MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.