Effects of sodium bicarbonate solution on hypergravity-induced Fos expression in neurons of the amygdala in rats: Implication of sodium bicarbonate therapy for vertigo

Objective

In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO₃) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO₃ inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats.

Methods

Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO₃ at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically.

Results

The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO₃ solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO₃ solution, compared to that in rats that received no drugs or saline.

Conclusion

Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO₃ suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO₃⁻ attenuates fear behavior [Cell 2009; 139: 1012–1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO₃ increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO₃ therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect.