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 language | English (US) |
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Pages (from-to) | 781-785 |
Number of pages | 5 |
Journal | Pharmacology, Biochemistry and Behavior |
Volume | 33 |
Issue number | 4 |
DOIs | |
State | Published - 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