Key role of 5-HT3 receptors in the nucleus tractus solitarii in cardiovagal stress reactivity

•The nucleus tractus solitarii (NTS) is the primary target site for reflex cardiovascular afferents.•Many neurotransmitters are present in the NTS, including glutamate, GABA, substance P and serotonin.•A functional interaction between 5-HT3, GABAA and NK1 receptors blocks the reflex parasympathetic component.•This functional interaction appears downstream to activation of the dorsolateral nucleus of the hypothalamus.•It is involved in both acute and chronic stress-induced reduction of parasympathetic tone.

Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS. This major influence on the ANS is also mediated by activation of several receptors in the NTS. In particular, the NTS is the central zone with the highest density of serotonin3 (5-HT3) receptors. In this review, we present evidence that 5-HT3 receptors in the NTS play a key role in one of the crucial homeostatic responses to acute and chronic stress: inhibitory modulation of the parasympathetic component of the ANS. The possible functional interactions of 5-HT3 receptors with GABAA and NK1 receptors in the NTS are also discussed.