SEROTONIN ANTAGONISTS AND CENTRAL HYPERTHERMIA PRODUCED BY BIOGENIC-AMINES IN CONSCIOUS RABBITS

Previous studies have shown that the hyperthermia produced by intracerebroventricular injection by 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 resembled cyproheptadine, 2-bromo LSD had almost the same effects as LSD and methysegide 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 an early component of th 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. Methiothepon 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 existance 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 of 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. © 1979.