Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses

J. Frank Nash*, Herbert Y. Meltzer, Gary A. Gudelsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The repeated administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg, twice daily for 14 days) significantly diminished hypothermia and corticosterone secretion induced by an acute challenge with the 5-HT1A agonist 8-OH-DPAT (0.1 mg/kg) when compared to the responses in animals treated chronically with the solvent vehicle. In contrast, the chronic administration of 5-MeODMT did not alter the magnitude of hyperthermia or corticosterone secretion induced by the acute administration of MK-212 (1.0 mg/kg). The repeated administration of the 5-HT2 agonist DOI (1.0 mg/kg, daily for 7 days) significantly reduced the increase in corticosterone, but not body temperature, produced by MK-212. Chronic treatment with DOI did not alter the hypothermia or increase in corticosterone secretion elicited by 8-OH-DPAT. These data are consistent with other evidence that these physiological effects of 8-OH-DPAT and MK-212 are mediated by 5-HT1A and 5-HT2 receptors, respectively. Thus, data presented in these studies are suggestive that the chronic administration of 5-MeODMT diminishes the responsiveness of 5-HT1A receptor-mediated changes in body temperature and cortiscosterone secretion without altering the responses mediated by 5-HT2 receptors. In contrast, the chronic administration of DOI selectively diminishes the magnitude of 5-HT2 receptor-mediated changes in corticosterone secretion without affecting the responsiveness of those receptors involved in thermoregulatory responses. These selective changes in receptor responsiveness following the chronic administration of these 5-HT agonists further establishes the independence of 5-HT1A and 5-HT2 receptor-mediated pharmacological effects.

Original languageEnglish (US)
Pages (from-to)781-785
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume33
Issue number4
DOIs
StatePublished - Aug 1989

Funding

ACKNOWLEDGEMENTS This work was supported, in part, by USPHS MH 41684, MH 41683, MH 41594 and grants from the Cleveland and Sawyer Foundations. J.F.N. is the recipient of a NARSAD Fellowship extension award. H.Y.M. is the recipient of a USPHS Research Career Scientist Award MH 47808. The authors thank Ms. Lee Mason for her excellent secretarial assistance in preparing this manuscript.

Keywords

  • 5-MeODMT
  • 8-OH-DPAT
  • Body temperature
  • Corticosterone
  • Cross-tolerance
  • MK-212
  • Tolerance

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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