EVIDENCE THAT ACTIVATION OF 5-HT2 RECEPTORS IN THE FOREBRAIN OF ANESTHETIZED CATS CAUSES SYMPATHOEXCITATION

1 The aim of the present experiments was to determine whether the effe cts of lateral ventricular application of 5-HT on cardiovascular and r espiratory variables in anaesthetized cats are mediated by forebrain 5 -HT2 receptors. This was carried out by determining whether the effect s of 5-HT are blocked by the 5-HT2 antagonist, cinanserin and if they are mimicked by the selective 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodoph enyl)-2-aminopropane (DOI). 2 Cats were anaesthetized with a mixture o f alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. The following cardiovascular and respirat ory variables were recorded: renal, splanchnic and cardiac sympathetic nerve activities, phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial conductance and tracheal pressure. Al drugs were administered via the lateral ventricle and the action of these a gonists was restricted to forebrain sites by a cannula placed in the A queduct of Sylvius. 3 Cumulative doses of 5-HT (10-160 nmol kg(-1)) an d DOI (80-320 nmol kg(-1)) injected into the lateral ventricle caused significant increases in blood pressure, heart rate, cardiac and splan chnic sympathetic nerve activity and a decrease in femoral arterial co nductance. DOI and 5-HT caused a greater increase in cardiac compared with splanchnic nerve activity and failed to change renal nerve activi ty. 5-HT but not DOI significantly increased the magnitude and the num ber of phrenic bursts as well as significantly increasing tracheal pre ssure. The effects of 5-HT also differed from DOI in that 5-HT evoked maximal presser and near maximal sympathoexcitatory effects after the first dose, whereas the presser and sympathoexcitatory effects of DOI were graded over the complete dose-range. 4 The 5-HT2 antagonist, cina nserin (265 nmol kg(-1), i.c.v.) caused significant falls in blood pre ssure, heart rate and cardiac nerve activity and an increase in femora l arterial conductance. Splanchnic and renal sympathetic nerve activit y, phrenic nerve activity and tracheal pressure were unaffected by cin anserin. After pretreatment with cinanserin all cardiovascular and res piratory effects of 5-HT were significantly attenuated. 5 It is conclu ded that in the cat, as DOI and 5-HT have similar effects on the cardi ovascular variables recorded and as the effects of 5-HT are blocked by cinanserin, 5-HT can act on 5-HT2 receptors located in the forebrain to cause differential sympathoexcitation and a rise in arterial blood pressure. Further, the sympathoexcitatory effects mediated by 5-HT2 re ceptors located in the forebrain differ from those located in the hind brain in that they mediate increases in cardiac nerve activity and hea rt rate and also have no effect on renal nerve activity.