Comet, Marie-Anne, Caroline Sévoz-Couche, Naïma Hanoun, Michel Hamon, and Raul Laguzzi. 5-HT-mediated inhibition of cardiovagal baroreceptor reflex response during defense reaction in the rat. Am J Physiol Heart Circ Physiol 287: H1641-H1649, 2004. First published May 27, 2004 10.1152 10. /ajpheart.01204.2003ous studies showed that the cardiac response of the baroreceptor reflex (bradycardia) is inhibited during the defense reaction evoked by direct electrical or chemical stimulation of the periaqueductal gray (dPAG) in the rat. Whether central serotonin and nucleus tractus solitarius (NTS) serotonin 3 (5-HT3) receptors might participate in this inhibition was investigated in urethane-anesthetized and atenolol-pretreated rats. Our results showed that both electrical and chemical stimulation of the dPAG produced a drastic reduction of the cardiovagal component of the baroreceptor reflex triggered by either intravenous administration of phenylephrine or aortic nerve stimulation. This inhibitory effect of dPAG stimulation on the baroreflex bradycardia was not observed in rats that had been pretreated with p-chlorophenylalanine (300 mg/kg ip daily for 3 days) to inhibit serotonin synthesis. Subsequent 5-hydroxytryptophan administration (60 mg/kg ip), which was used to restore serotonin synthesis, allowed the inhibitory effect of dPAG stimulation on both aortic and phenylephrine-induced cardiac reflex responses to be recovered in p-chlorophenylalanine-pretreated rats. On the other hand, in nonpretreated rats, the inhibitory effect of dPAG stimulation on the cardiac baroreflex response could be markedly reduced by prior intra-NTS microinjection of granisetron, a 5-HT 3 receptor antagonist, or bicuculline, a GABAA receptor antagonist. These results show that serotonin plays a key role in the dPAG stimulation-induced inhibition of the cardiovagal baroreceptor reflex response. Moreover, they support the idea that 5-HT 3 and GABAA receptors in the NTS contribute downstream to the inhibition of the baroreflex response caused by dPAG stimulation. nucleus tractus solitarius; serotonin3 receptors; GABAA receptors; defense/attack MUCH EVIDENCE indicates that serotonin (5-hydroxytryptamine; 5-HT) plays a modulatory role in the central control of cardiovascular parameters (28, 32), notably through actions at the level of the nucleus tractus solitarius (NTS) (13, 15), a key structure for the integration of baroreceptor and other peripheral and central messages involved in the homeostatic control of blood pressure (BP) and heart rate (HR) (9,11,19). In particular, serotonin 3 (5-HT 3 ) receptor stimulation specifically in the NTS was shown to elicit a transitory increase in BP and to block the cardiovagal component (bradycardia) of the baroreceptor reflex (15,25). Interestingly, transient hypertension and inhibition of the cardiac baroreceptor reflex response are also the cardiovascular changes that accompany the defense reaction and other behavioral responses to various stressful conditions (16,17).Inhibition of the baroreceptor...