Activation of nucleus tractus solitarius 5-HT2A but not other 5-HT2 receptor subtypes inhibits the sympathetic activity in rats

• Published in: The European journal of neuroscience 2007-07, Vol.26 (2), p.345-354
• Main Authors: Comet, M.-A., Bernard, J. F., Hamon, M., Laguzzi, R., Sévoz-Couche, C.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Atenolol - pharmacology; Atropine Derivatives - pharmacology; baroreflex; Baroreflex - drug effects; Baroreflex - physiology; Blood Pressure - drug effects; brainstem; Heart Rate - drug effects; Indoles - pharmacology; Life Sciences; Male; Microinjections; Pyrazines - pharmacology; rat; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A - drug effects; Receptor, Serotonin, 5-HT2A - physiology; rostroventrolateral medulla; serotonergic receptors; Serotonin Receptor Agonists - pharmacology; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Thiophenes - pharmacology; unit activity
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2007.05673.x

Our first aim was to elucidate the mechanisms underlying the hypotensive response elicited by 5‐HT2 receptor activation in the nucleus tractus solitarius (NTS). In pentobarbitone‐anaesthetized rats, intra‐NTS administration of 2,5‐dimethoxy‐4‐iodoamphetamine (DOI), a wide spectrum 5‐HT2 receptor agonist, but not an antagonist of selective 5‐HT2B and 5‐HT2C receptors, produced a decrease in blood pressure and heart rate. The maximal cardiovascular changes obtained by DOI (0.5 pmol) could be almost completely abolished by prior intra‐NTS microinjection (10 pmol) of MDL‐100907, a selective 5‐HT2A receptor antagonist, but not by 5‐HT2B or 5‐HT2C receptor antagonists. In addition, using extracellular recordings we found that the large majority of identified cardiovascular rostroventrolateral medulla (RVLM) neurons were almost totally inhibited by NTS 5‐HT2A receptor stimulation. We then investigated whether intra‐NTS administration of a subthreshold dose (0.05 pmol) of DOI, known to facilitate the cardiovagal component of the baroreflex, could also modulate the sympathoinhibitory component of this reflex. These experiments showed that neither the decrease in the activity of the cardiovascular RVLM neurons and lumbar sympathetic nerve activities produced by aortic occlusion (gain of the baroreflex), nor the hypotensive response elicited by aortic nerve stimulation, were potentiated by the microinjection of DOI under such conditions. These data show that activation of 5‐HT2A, but not 5‐HT2B or 5‐HT2C, receptors, located on NTS neurons, elicits depressor and bradycardic responses, and that this 5‐HT2A‐mediated hypotension is produced via the inhibition of RVLM cardiovascular neurons. In addition, NTS 5‐HT2A receptor activation facilitates the cardiac but not the sympathetic baroreflex response.