cinanserin and Fever

Methergoline, an antagonist of cerebral serotonin receptors, has been shown to significantly reduce the rise in rectal temperature (Tre) produced by the intracerebral microinjection of beta-endorphin. In this study the role of serotonin in the increase in Tre elicited by beta-endorphin was further examined using three additional serotonin antagonists. beta-Endorphin was administered twice to rats using a crossover design in which half of the animals were first pretreated with the vehicle solution and half with the antagonist. Serotonin antagonists used were: methergoline, methysergide, cinanserin and cyproheptadine. Although methergoline did cause a marked reduction in the beta-endorphin-induced rise in Tre, neither methysergide, nor cinanserin, nor cyproheptadine produced a marked reduction in the hyperthermia. Since methergoline also interacts with the dopamine receptor, the effect of a dopamine antagonist, haloperidol, on the endorphin-evoked response was also examined. Haloperidol failed to attenuate the rise in Tre. The reason for the apparent discrepancy in the action of these serotonin antagonists is unclear. Further research may reveal distinct subpopulations of serotonin receptors at which these antagonists exert differential effects.

Topics: Animals; beta-Endorphin; Body Temperature; Body Temperature Regulation; Cinanserin; Endorphins; Fever; Haloperidol; Metergoline; Methysergide; Rats; Serotonin Antagonists

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.

Topics: Animals; Body Temperature; Cinanserin; Dopamine; Fever; Lysergic Acid Diethylamide; Male; Methiothepin; Methysergide; Norepinephrine; Phenothiazines; Rabbits; Serotonin; Serotonin Antagonists

Fenfluramine produces dose-related hyperthermia and behavioral stimulation in rabbits following intravenous administration. Both responses were antagonized by pretreatment with cinanserin, cyproheptadine, or fluxetine. Methergoline likewise abolished the stimulatory effect of fenfluramine and produced a partial blockade of the hyperthermia. Haloperidol was ineffective as a fenfluramine antagonist. This study demonstrates that fenfluramine-induced hyperthermia and stimulation in the rabbit result from an indirect action upon serotonergic receptors.

Topics: Animals; Behavior, Animal; Body Temperature; Cinanserin; Cyproheptadine; Dose-Response Relationship, Drug; Fenfluramine; Fever; Haloperidol; Male; Metergoline; Phenyl Ethers; Propylamines; Rabbits; Receptors, Adrenergic; Receptors, Drug; Serotonin

Topics: 5-Hydroxytryptophan; Acetylcholine; Blood Pressure; Bronchi; Cinanserin; Dextrans; Edema; Female; Fever; Gastrointestinal Tract; Guinea Pigs; Histamine; Humans; Lysergic Acid Diethylamide; Maleates; Pharmacology; Phenobarbital; Rabbits; Rats; Research; Selective Serotonin Reuptake Inhibitors; Serotonin; Toxicology; Uterus