Temporal change in NMDA receptor signaling and GABAA receptor exypression in rat caudal vestibular nucleus during motion sickness habituation

Repeated exposure to a provocative motion stimulus leads to motion sickness habituation indicative of the existence of central processes to counteract the disturbing properties of the imposed motion. In the present study, we attempt to investigate whether NMDA and GABAA receptors in rat caudal vestibular nucleus neurons are involved in motion sickness habituation induced by repeated Ferris-wheel like rotation in daily session (2 h/d). We showed that defecation response increased and spontaneous locomotion decreased within 4 sessions (sickness phase). They recovered back to the control level after 7 sessions (habituation phase). Western blot analysis found that NMDA receptor signal molecules: calmodulin protein kinase II and cAMP response element-binding protein (CREB) were both activated during sickness phase, while a prolonged CREB activation was also observed during habituation phase. Real-time quantitative PCR revealed an increase in c-fos and a decrease in Arc mRNA level during sickness phase. We also found an increase in GABAA receptor α1 subunit (GABAA α1) protein level in this stage. These results suggested that altered NMDA receptor signaling and GABAA receptor expression level in caudal vestibular nucleus were associated with motion sickness habituation. Furthermore, immunofluorescence and confocal laser scanning microscopy showed that the number of GABAA α1 immunolabeled neurons in caudal vestibular nucleus increased while the number of GABAA α1/Arc double labeled neurons and the average amount of Arc particle in soma of these neurons decreased during sickness phase. It suggested that GABAA receptor level might be negatively regulated by Arc protein in caudal vestibular nucleus neurons.

► Daily Ferris-wheel like rotation induced motion sickness habituation in adult rats. ► We investigated NMDAR signaling and GABAAR α1 subunit level in caudal vestibular nucleus. ► Daily rotation led to gradual decrease in NMDAR signaling and GABAAR α1 subunit level. ► GABAAR α1 subunit was co-expressed with and negatively regulated by Arc protein. ► Both NMDAR and GABAAR might be associated with motion sickness habituation achievement.