Previous studies have shown that the
hyperthermia produced by intracerebroventricular injection of
5-hydroxytryptamine (5-HT) to conscious rabbits was antagonized by
cyproheptadine and increased by
LSD. Other putative antagonists, i.e.
cinanserin,
methiothepin, 2-bromo
LSD,
methysergide and dimetiotazine are investigated in the present report.
Cinanserin and
methiothepin resembeld
cyproheptadine, 2-bromo
LSD had almost the same effects as
LSD and
methysergide exhibited a mixed pattern of action, being depressant or potentiating as a function of dose. Dimetiotazine had no specific action.
Cinanserin, however, differed from
cyproheptadine in selectively antagonizing and early component of the
5-HT rise, unmasking an important fall and leaving a late hyperthermic component unaffected, thus disclosing three distinct effects of
5-HT action. The
cinanserin,
methiothepin and
methysergide antagonism of the 5-HT-induced temperature rise was greater than the antagonism of the
noradrenaline (NA)-induced rise.
Methiothepin and
methysergide inhibited both the
5-HT and DA
hyperthermia;
cinanserin--like
cyproheptadine--was more effective on the
5-HT rise. The potentiation of the
5-HT temperature rise by 2-bromo
LSD and
methysergide was more developed than was the potentiation of the NA and DA rises. The effects of the drugs studied on
5-HT action argue in favour of the existence of several types of central
5-HT receptors. The dissociation observed between the antagonism to
5-HT and that to DA does not favour a mediation of DA
hyperthermia by 5-HT; antiserotonin drug antagonism of DA
hyperthermia is more simply accounted for by interactions at the level fo specific DA receptors. The potentiation of the 5-HT-induced temperature rise by 2-bromo
LSD and
methysergide might result from an antagonism of the hypothermic component. As with
LSD, 2-bromo
LSD and
methysergide alone also produced
hyperthermia, the origin of which is briefly discussed.