Adrenocorticotropic hormone secretion in rats induced by stimulation with serotonergic compounds

The serotonin receptors involved in the secretion of adrenocorticotropin ho rmone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5-HT), 5-hydroxytryptophan (5-HTP) in combination with the s erotonin reuptake inhibitor fluoxetine (Flx), or of the 5-HT agonists 8-OH- DPAT (5-HT1A), 5-carboxamido-tryptamine (5-HT1A+1B+5A+7), RU 24969 (5-HT1B1A), DOI (5-HT2A+2C), S-alpha-methyl-5-HT (5-HT2A+2B+2C), MK212 (5-HT2B+2C) , or methyl-chlorophenyl-piperazine (5-HT2A+2C) dose-dependently stimulated ACTH secretion, The 5-HT3 agonist 2-methyl-5-HT had no effect. Administrat ion of a 5-HT1 agonist in combination with any of the 5-HT2 agonists DOI, S -alpha-methyl-5-HT or MK212 had an additive effect on the plasma concentrat ion of ACTH. The ACTH stimulating effect of each of the 5-HT agonists was i nhibited by pretreatment with antagonists with corresponding 5-HT receptor affinity. The ACTH response to 5-HT or 5-HTP/Flx was inhibited by injection with the 5-HT1A+2A+2C+5A+7 antagonist methysergide, the 5-HT2A antagonist ketanserine and the 5-HT2C+2A antagonist LY 53857, The 5-HT1A antagonist WA Y 100635 enhanced 5-HT- and 5-HTP/Flx-induced ACTH secretion, suggesting a presynaptic 5-HT1A autoreceptor effect of the drug. The 5-HT3 antagonist on dansetrone had no effect on the either of the 5-HT agonists, The 5-HT3+4 an tagonist tropisetrone attenuated the effect of 5-HTP/Flx, which may suggest a stimulation of ACTH secretion via 5-HT4 receptors, It is concluded that 5-HT1A, 5-HT2A+2C, and to a lesser extent 5-HT1B receptors, but not 5-HT3 r eceptors are involved in the effects of serotonin agonists on ACTH secretio n. Furthermore, an involvement of the 5-HT5A and the 5-HT7 receptor is poss ible.