Central 5-HT pathways acting via 5-HT_1A, 5-HT₃ and 5-HT₇ receptors play a critical role in the regulation of cardiovascular reflexes (Ramage & Villalón, 2008). 5-HT_1A receptors are involved in the reflex regulation of parasympathetic (vagal) control of the heart and data indicates that the predominant location of these receptors is within the nucleus ambiguus. In contrast, 5-HT₃ receptors are involved in afferent processing within the nucleus tractus solitarius (NTS) where their activation involves the release of glutamate, probably to some extent from glia. However, the location(s) of 5-HT₇ receptors within the cardiovascular reflex pathways (Kellett et al. 2005) is unknown. The present study was carried out to investigate the effects of the 5 HT₇ receptors non-selective agonist 5-carboxamidotryptamine (5-CT) and the selective antagonist SB 258719 (Forbes et al. 1998) applied ionophoretically on the ongoing and vagal-evoked activity of NTS neurones. Sprague-Dawley rats (250-330g) were anaesthetized with sodium pentobarbitone (60 mg kg^-1, i.v.), neuromuscular blocked (α-bungarotoxin 150 μg kg^-1, i.v.) and artificially ventilated with O₂-enriched air. NTS neuronal activity was recorded as previously described (Wang et al., 1998). Depth of anaesthesia was assessed by the stability of arterial blood pressure and heart rate following a noxious stimulus and additional anaesthetic was given when necessary. NTS neurones were identified by orthodromic excitation from stimulation of the vagus nerve (10-400 μA, 0.2-1.0 ms, 0.5-1.0 Hz). Cardiopulmonary afferents were stimulated by right atrial injection of phenylbiguanide (PBG, 12-24 μg kg^-1). All values are means ± S.E.M. Comparisons between mean were made with Student’s paired t-test. P < 0.05 was considered to be significant. In 18/76 neurons 5-CT (40-100nA; pH 4) significantly increased baseline firing rate from a mean of 3.2 ± 0.5 to 5.1 ± 0.5 spikes s^-1. SB 258719 (100-150nA; pH 4) alone did not affect background activity. In 9 neurones SB 258719 (100-150nA) significantly blocked the increase in activity evoked by 5-CT (5.0 ± 0.9 to 4.9 ± 0.7 cf. 4.5 ± 0.8 to 6.3 ± 0.8). SB 258719 also significantly decreased vagal-afferents evoked activity from 17 ± 1 to 8 ± 1.3 spikes 20 sweeps^-1 in 20/35 tested. Out of these, 5-CT excited 3 neurons, inhibited 7 and had no effect on the remaining 10 neurons. In 2 of 3 neurones 5-CT exciation was blocked by SB 258719 at the same current that attenuated the evoked activity. Further cardiopulmonary afferent-evoked activity was also significantly inhibited by SB 258719 in 4 out of 6 neurons (66%) tested. 5-CT also had an inhibitory action, and in 9 neurons tested this was unaffected by SB 258719. This data indicates that 5-HT₇ receptors within NTS are involved in vagal afferent processing.