Ik. Anderson et al., EVIDENCE THAT ACTIVATION OF 5-HT2 RECEPTORS IN THE FOREBRAIN OF ANESTHETIZED CATS CAUSES SYMPATHOEXCITATION, British Journal of Pharmacology, 116(2), 1995, pp. 1751-1756
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.