PRESSOR EFFECTS FOLLOWING MICROINJECTION OF 5-HT1A RECEPTOR AGONISTS INTO THE RAPHE OBSCURUS OF THE ANESTHETIZED RAT

1 The effects of electrical stimulation and microinjections (90 nl) of the 5-HT1A receptor agonists, flesinoxan and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and glutamate into the raphe obscurus on blood pressure, heart rate and phrenic nerve activity (central inspiratory drive) were investigated in rats anaesthetized with alpha-chloralose. 2 Electrical stimulation of the raphe obscurus caused a rise in blood pressure which was associated with bradycardia, while glutamate (2.7 nmol) caused only a rise in blood pressure. 3 Flesinoxan (1.3 nmol) and 8-OH-DPAT (0.7 nmol) increased blood pressure by 9 +/- 1 and 14 +/- 2 mmHg, respectively and did not affect heart rate. For both agonists the effect on blood pressure was shown to be dose-dependent; again no effect on the heart rate was observed over the dose-ranges chosen. 4 Microinjections of the non-selective 5-HT1A receptor antagonists, (+/-)-pindolol (2.7 nmol) or methiothepin (5.2 nmol), into the raphe obscurus prevented the increase in blood pressure caused by microinjection of flesinoxan. However, (+/-)-pindolol caused a sustained rise in blood pressure of 15 +/- 1 mmHg while methiothepin caused a transient rise in blood pressure. Neither drugs affected heart rate. The ability of methiothepin to attenuate the pressor effect of flesinoxan was found to be partially reversed after 30 min. 5 It is suggested that activation of 5-HT1A receptors within the raphe obscurus can cause sympatho-excitation.