Effects of hypergravity on histamine H1 receptor mRNA expression in hypothalamus and brainstem of rats: implications for development of motion sickness.
CONCLUSIONS
The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness.


OBJECTIVE
We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression.


METHODS
For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats.


RESULTS
After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.
Sato
Go
G
Department of Otolaryngology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Japan. go-sato@clin.med.tokushima-u.ac.jp
Uno
Atsuhiko
A
Horii
Arata
A
Umehara
Hayato
H
Kitamura
Yoshiaki
Y
Sekine
Kazunori
K
Tamura
Koichi
K
Fukui
Hiroyuki
H
Takeda
Noriaki
N
D000818:Animals; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D018471:Hypergravity / Q000009:adverse effects*; D007031:Hypothalamus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009041:Motion Sickness / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D012333:RNA, Messenger; D011969:Receptors, Histamine H1