Central 5-HT7 receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats

5-Hydroxytryptamine (5-HT; serotonin) -containing neurones contribute to reflex activation of parasympathetic outflow in a number of species, but the 5-HT receptors mediating these effects have yet to be fully determined. The present experiments demonstrate that central 5-HT7 receptors are involved in the vagal bradycardia evoked during the cardiopulmonary reflex, baroreflexes and the chemoreflex, as well as other autonomic changes caused by these reflexes. The experiments examined the effects of the selective 5-HT7 receptor antagonists SB-269970 and SB-656104 on these reflexes. For the cardiopulmonary reflex, when compared to time-matched vehicle control experiments, intracisternal application of SB-269970 (30-300 mug kg(-1), I.C.) dose-dependently attenuated the evoked bradycardia. At the highest dose, SB-269970 also attenuated the reflex hypotension and sympathoinhibition. The structurally different 5-HT7 receptor antagonist SB-656104 (100 mug kg(-1), I.C.) similarly attenuated the reflex bradycardia and hypotension. SB-269970 (100 mug kg(-1), I.C.) also attenuated the bradycardias evoked by electrical stimulation of aortic nerve afferents and the baroreflex evoked by the pressor response to phenylephrine (3-25 mug kg(-1), i.v.). The gain of the baroreflex was also significantly attenuated (0.15 +/- 0.06 versus 0.34 +/- 0.06 ms mmHg(-1)). Finally, SB-269970 (100 mug kg(-1), I.C.) significantly attenuated both the bradycardia and sympathoexcitation evoked by the chemoreflex. These data indicate that central 5-HT7 receptors play an important facilitatory role in the reflex activation of vagal outflow to the heart.