GABAergic neurons in the dorsal raphe nucleus that express 5-HT3A receptors participate in responses to stress hormones.

Abstract The dorsal raphe nucleus (DRN) participates in stress responses and in mood regulation via its ascending release of serotonin (5-HT) onto neural circuits within the forebrain. Although the 5-HT DRN region is easily defined via 5-HT-expressing DRN neurons, the neuroarchitecture and microcircuitry that confer its multifunctionality have remained incompletely understood and have required further investigation. In this present study, neurochemical interactions within different subregions of the rat DRN were precisely analyzed. We found that 97.5% of GABAergic neurons in the DRN expressed ionotropic 5-HT3A receptors (5-HT3ARs), whereas there were only rare parvalbumin (PV)-positive or somatostatin (SOM)-positive GABAergic neurons. Furthermore, corticosterone administration into male rats as a rodent model of depression induced significantly higher c-Fos expression in 5-HT3AR-positive GABAergic neurons compared to that in 5-HT neurons within the DRN. Taken together, our findings suggest that 5-HT3AR-positive GABAergic neurons in the DRN participate in responses to stress hormones in a rat model of depression.