The dorsomedial hypothalamic nucleus (DMH) mediates the cardiovascular response to stimuli such as air jet stress or cold stress (1). The sympathoexcitatory vasomotor and cardiac components of the DMH-evoked response are dependent upon neurons in the rostral ventrolateral medulla and raphe pallidus in the medulla (1,2). Both of these regions contain 5-HT1A receptors. Intravenous administration of the selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) centrally inhibits sympathetically mediated cutaneous vasoconstriction induced by cold stress (3). The aim of this study was to investigate the effect of systemic administration of 8OH-DPAT on the cardiovascular response evoked by DMH activation and, as a control, on the reflex responses to chemoreceptor and baroreceptor stimulation. Sprague-Dawley rats (body weight 410-480 g) were anaesthetized with urethane (1.3 g/kg, i.v. after induction with 2% isoflurane). Bicuculline microinjections (10 pmol in 20nl) into the DMH resulted in a modest increase in mean arterial pressure (MAP; 16 ± 2 mmHg), heart rate (HR; 89 ± 13 bpm) and renal sympathetic nerve activity (RSNA; 47 ± 4% of baseline). Intravenous injection of 8-OH-DPAT (0.1 mg/kg) resulted in small but significant decreases in resting MAP (12 ± 1 mmHg, P<0.05) and HR (32 ± 7 bpm, P<0.05) and had no significant effect on resting RSNA (change 0 ± 3% baseline), but greatly reduced the increases in MAP, HR and RSNA evoked by DMH activation (to 3 ± 2 mmHg, 15 ± 4 bpm and 4 ± 2%, respectively; P0.5 in all cases) to those observed before 8-OH-DPAT administration. Administration of 8-OH-DPAT did not alter either the increase in RSNA evoked by chemoreceptor stimulation with sodium cyanide (0.1 mg/kg, i.v.) or the cardiac-related component of the RSNA response. The results indicate that activation of 5-HT1A receptor blocks the cardiovascular response evoked from the DMH but does not affect sympathetic vasomotor tone or chemoreceptor and baroreceptor reflexes. All animals were humanely killed at the end of the experiments.