Role of various 5-HT receptor subtypes in mediating neuroendocrine effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats.
The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. Pretreatment with metergoline (serotonin, 5-HT1/5-HT2 antagonist), ritanserin and mianserin (5-HT2A/5-HT2C antagonists) significantly attenuated DOM-induced increases in prolactin, ACTH and corticosterone, whereas mesulergine (5-HT2A/5-HT2C antagonist) pretreatment significantly attenuated DOM-induced increases in plasma prolactin and ACTH but not corticosterone. Pretreatment with propranolol (beta adrenoceptor antagonist that also has high binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 and ondansetron (5-HT3 antagonists) attenuated DOM's effect on plasma prolactin, but did not attenuate DOM-induced increases in either ACTH or corticosterone. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced increases in ACTH but not corticosterone. These findings demonstrate involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. DOM does not affect growth hormone secretion in rats.
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland.
C S
CS
Aulakh
P
P
Mazzola-Pomietto
J L
JL
Hill
D L
DL
Murphy
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D008297:Male; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D014326:Tropanes / Q000494:pharmacology
D011985:Receptors, Serotonin; D014326:Tropanes; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; C042253:bemesetron; D003345:Corticosterone