Age-related changes in the serotonin 2A receptor in the hypoglossal nucleus of male and female rats.

Hypoglossal motoneuron output to the genioglossus muscle contributes to upper airway patency. Serotonin (5HT) plays an important role in regulating hypoglossal motoneuron excitability via serotonin 2A receptors (5HT(2A)). The purpose of this study was to investigate whether there are age-associated changes in 5HT(2A) receptor expression in the hypoglossal nucleus of male and female rats. The brains of young, middle-aged and old F344 rats were sectioned, reacted immunocytochemically for the presence of 5HT(2A) receptor, and the staining density quantified. The estrus stage of female rats was determined and circulating sex hormone levels measured and correlated with 5HT(2A) levels. The results show that there was significantly greater 5HT(2A) receptor immunoreactivity in the hypoglossal nucleus of female than of male rats. With increasing age, there was an increase in 5HT(2A) receptor immunoreactivity in the hypoglossal nucleus of female rats, whereas no age-associated changes were observed in male rats. Previous studies have shown a reduction in 5HT-dependent respiratory plasticity and an age-associated decrease in 5HT in the hypoglossal nucleus in male but not female rats. Data from the present study suggest that aging male rats fail to compensate adequately for reduced 5HT in the hypoglossal nucleus by upregulating the expression of the 5HT(2A) receptor.