The Key Role of Medullary 5-HT3 Receptors in the Serotonin-Mediated Neural Control of Cardiovascular Function

The baroreceptor reflex plays a crucial role in the homeostatic control of cardiovascular parameters. In the central nervous system, the nucleus of the tractus solitarius (NTS) is critically involved in cardiovascular reflex control because it is both the first site of termination of glutamatergic baroreceptor afferent fibres and an important integrative area for the sensory afferent signals reaching the brainstem. In addition to glutamate, the NTS contains numerous neurotransmitters that could participate in the modulations of the baroreceptor reflex sensitivity which occur under various physiological conditions. In particular, a large body of evidence indicates that serotonin plays a modulatory role in the central control of blood pressure, especially at the level of the NTS, which is innervated by both central and peripheral serotonergic fibres. Indeed, serotonin exerts multiple cardiovascular influences through the activation of several receptors in the NTS. Actually, the NTS is the central area endowed with the highest density of serotonin3 (5-HT3) receptors whose stimulation triggers all the adaptive cardiovascular changes normally associated with behavioural responses to various stressful conditions. In this review, we first assess the current knowledge about the mechanisms underlying the cardiovascular effects of the specific activation of serotonergic receptors in the NTS. Secondly, we describe evidence that, in the NTS, 5-HT3 receptors play a key role in one of the crucial homeostatic responses that characterise the defence reaction: the inhibitory modulation of the parasympathetic cardiac component of the baroreceptor reflex. The possible functional interactions of 5-HT3 receptors with GABAA, NK1 and NMDA receptors within the NTS are also discussed.