Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses.
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 corticosterone 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.
Nash
J F
JF
Department of Psychiatry and Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Meltzer
H Y
HY
Gudelsky
G A
GA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008732:Methoxydimethyltryptamines / Q000008:administration & dosage / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
D000662:Amphetamines; D008732:Methoxydimethyltryptamines; D009281:Naphthalenes; D011719:Pyrazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone