Central 5-HT-containing pathways are known to play a physiological role in the regulation of the cardiovascular system (Ramage & Villalón, 2008). Of the 14 different receptor subtypes, 5-HT1A, 5-HT2 and 5-HT3 have been implicated in this regulation and more recently 5-HT7 receptors. The present experiments were carried out to further investigate the role of 5-HT7 receptors by examining the effects of the non-selective 5-HT7 agonist 5-CT and the selective antagonists SB-269970 and SB-258719 (Hagen et al. 2000) given intracerebroventricularly (i.c.v.). Male Sprague-Dawley rats (230-270g) were anaesthetized with α-chloralose (100 mg kg-1, i.v.), neuromuscular blocked (α-bungarotoxin 30 µg, i.v.) and artificially ventilated. Recordings were made of arterial blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RNA). Depth of anaesthesia was assessed by the stability of BP and HR following a noxious stimulus and additional anaesthetic was given when necessary. Changes were compared with saline (5 μl) by two-way ANOVA and the least significant difference test. P<0.05 was considered to be significant. All values are means ± S.E.M. Cumulative doses of 5-CT (0.01-1 µg kg-1; n=5) caused significant dose related increases in RNA, BP and HR, although at the highest dose (10 µg kg-1) BP fell (24 ± 3 mmHg). Pretreatment for 20 min (100 µg kg-1, n=4) with either SB-269970 or SB-258719 attenuated the effects of 5-CT. Both antagonists caused initial falls in BP (13 ± 2 & 19 ± 2 mmHg) and increases in RNA (27 ± 4 & 59 ± 11%) as did 10 µg kg-1 of SB-258719, which also blocked the effects of 5-CT. Cumulative doses of either antagonist (0.1-100 µg kg-1, n=4) caused at the highest two doses (10 & 100 µg kg-1) renal sympathoexcitation reaching 151 ± 30 & 83 ± 21%. For SB-258719 this was associated with falls in BP, while for SB-269970 this only occurred at 100 µg kg-1. HR was unaffected. Pretreatment with SB-269970 (100 µg kg-1, n=4) attenuated these effects of SB-258719. Interestingly, SB-269970 i.v. (100 µg kg-1, n=4) had little effect on RNA and BP as did microinjections of SB-269970 (10 µg kg-1, 1 µl, n=4) into the dorsal raphé. The data suggests that the activation of 5-HT7 receptors accessed by i.c.v causes sympathoexcitation and indicates that at this level of the brain the antagonists are having a partial agonist action. Interestingly, when SB-269970 was given intracisternally there was no effect (Kellett et al. 2005). The ability of these ligands to cause a fall in blood pressure is difficult to explain. For 5-CT this could be due to a peripheral action but this would not apply to the antagonists. Therefore it is suggested that these falls may involve the central release of a vasodilator peptide. The exact central site/s these effects are being mediated by remain to be determined.