Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors

G. A. Gudelsky*, J. I. Koenig, H. Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

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°C was observed 30min 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°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 hypothermie 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 hypothermie 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. It also was found that treatment of rats with the 5-HT2 antagonists ketanserin or pirenperone alone resulted in a decrease in body temperature, whereas the administration of pindolol produced an increase in body temperature. On the basis of the present findings, it is concluded that the hyperthermic responses following the administration of MK-212 are mediated by central 5-HT2 receptors and that the hypothermic responses to 8-OH-DPAT involve the activation of central 5-HT1A receptors. The differential effects of 5-MeODMT on body temperature suggest that this indoleamine can activate both subtypes of 5-HT receptor.

Original languageEnglish (US)
Pages (from-to)1307-1313
Number of pages7
JournalNeuropharmacology
Volume25
Issue number12
DOIs
StatePublished - Dec 1986

Keywords

  • 5-HT
  • 8-OH-DPAT
  • body temperature
  • receptor subtypes

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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