Serotonin antagonists and central hyperthermia produced by biogenic amines in conscious rabbits.
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.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002928:Cinanserin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010640:Phenothiazines; D012702:Serotonin Antagonists; D012701:Serotonin; D008719:Methiothepin; D008238:Lysergic Acid Diethylamide; D002928:Cinanserin; D004298:Dopamine; D009638:Norepinephrine; D008784:Methysergide