Serotonergic stimulation of pituitary-adrenal activity in the mouse.
Female CF1 mice were given L-5-hydroxytryptophan (5-HTP), quipazine, or  6-methoxy-1,2,3,4-beta-carboline (6-MeO-THBC) in conjunction with various serotonergic drugs to determine if the pituitary-adrenal stimulation produced by the former compounds is serotonergically mediated. Corticosterone (CS) responses to 5-HTP were uninfluenced by pretreatment with a tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA), but were significantly potentiated by a serotonin (5-HT) reuptake inhibitor (Lilly 110140), attenuated by two 5-HT receptor blockers, cyproheptadine and methergoline, and almost completely abolished by 2 extracerebral aromatic L-amino acid decarboxylase inhibitors, MK 486 and a low dose of Ro 4-4602. It was also established that L-tryptophan could stimulate pituitary-adrenal activity in animals pretreated with the monoamine oxidase (MAO) inhibitor pargyline. Serotonergic drugs were generally not as effective in modulating the responses to quipazine and 6-MeO-THBC. It is concluded that (1) 5-HTP stimulates pituitary-adrenal activity in mice by being converted to 5-HT and acting on 1 or more groups of serotonergic receptors; (2) these receptors are located either in an area of the brain outside of the blood-brain barrier such as the median eminence or in a peripheral tissue(s); (3) tryptophan-derived 5-HT can stimulate these receptors, but only if allowed to accumulate by inhibiting its catabolism; and (4) it is not yet clear whether pituitary-adrenal responses to quipazine and 6-MeO-THBC are mediated by a serotonergic mechanism.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D003533:Cyproheptadine / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008711:Metergoline / Q000494:pharmacology; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
D002243:Carbolines; D007211:Indoles; D010647:Phenyl Ethers; D011437:Propylamines; D011804:Quinolines; D008711:Metergoline; D003533:Cyproheptadine; D011814:Quipazine; D013134:Spiperone; D001545:Benserazide; D001285:Atropine; D014364:Tryptophan; D010293:Pargyline; D006916:5-Hydroxytryptophan; D002230:Carbidopa; D010134:Fenclonine; D003345:Corticosterone