Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors.
The effects of serotonergic agonists and antagonists on the body temperatures of rats were investigated. The administration of the serotonin (5-HT) agonist 6-chloro-2(1-piperazinyl)-pyrazine (MK-212) produced a dose-related increase in body temperature. A maximal increase in body temperature of approx. 1.1 degrees C was observed 30 min after the administration of 3 mg/kg of MK-212. In contrast, administration of the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in marked, dose-related hypothermic responses. Body temperatures were decreased approx. 3 degrees C 30 min after an injection of 0.3 mg/kg of 8-OH-DPAT. Body temperatures were affected differentially by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Large doses (3-10 mg/kg) of 5-MeODMT elicited hyperthermic responses, whereas small doses (0.5-1.0 mg/kg) produced hypothermic responses. Treatment of rats with ketanserin (3 mg/kg) completely prevented the hyperthermic effects of 5-MeODMT, and, in fact, converted a hyperthermic response to 5-MeODMT into a marked hypothermic response. Ketanserin (0.1-1.0 mg/kg) selectively antagonized the hyperthermic response to MK-212 but did not alter the hypothermic effect of 8-OH-DPAT. Mianserin (10 mg/kg) and pirenperone (0.03 mg/kg) also selectively antagonized hyperthermia induced by MK-212. In contrast, pindolol (0.03-0.1 mg/kg) and methiothepin (10 mg/kg) selectively antagonized hypothermia induced by 8-OH-DPAT but did not alter hyperthermia induced by MK-212. Spiperone (0.1-3 mg/kg) and pizotifen (10 mg/kg) attenuated the effects of both 8-OH-DPAT and MK-212. Xylamidine, a peripheral 5-HT antagonist, had no significant effect on hyperthermia induced by MK-212 or hypothermia induced by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D010880:Piperidines; D011719:Pyrazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D013134:Spiperone; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D010869:Pindolol; C034177:pirenperone