Injection of L-glutamate into the insular cortex produces sleep apnea and serotonin reduction in rats.

ABSTRACT

PURPOSE: Obstructive sleep apnea (OSA) is primarily characterized by repetitive episodes of complete or partial obstruction of airflow during sleep. The neuronal and cellular mechanisms underlying this process are not fully understood, although the focus of some studies is on putative serotonin (5-HT) mechanisms, and serotonergic therapy may be beneficial to OSA patients. This study aimed to demonstrate possible changes in 5-HT associated with induction of OSA in a rat model. METHODS: Apnea was induced in rats by injection of L-glutamate (L-Glu) into the insular cortex. We examined changes in (1) simultaneous genioglossus and diaphragm EMG activity; and (2) peripheral and cerebral levels of 5-HT, by histology. RESULTS: Injection of L-glutamate (L-Glu) into the insular cortex induced apnea in the rats. L-Glu stimulation of the insular cortex also produced significant reductions in plasma 5-HT levels and the expression of 5-HT in the brainstem. In addition, lower activity was observed in the GG and a higher activity was observed in the diaphragm, as compared to controls. CONCLUSION: Data indicate that L-Glu stimulation of the insular cortex simulates the electrical activity of the genioglossus muscle and diaphragm in sleep apnea, and contributes to reduced peripheral and cerebral 5-HT levels in rats. The results of our study suggest that 5-HT may play a role in the pathogenesis of OSA.