Adrenocorticotropic Hormone Secretion in Rats Induced by Stimulation with Serotonergic Compounds

The serotonin receptors involved in the secretion of adrenocorticotropin hormone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5‐HT), 5‐hydroxytryptophan (5‐HTP) in combination with the serotonin reuptake inhibitor fluoxetine (Flx), or of the 5‐HT agonists 8‐OH‐DPAT (5‐HT 1A ), 5‐carboxamido‐tryptamine (5‐HT 1A+1B+5A+7 ), RU 24969 (5‐HT 1B+1A ), DOI (5‐HT 2A+2C ), S‐ α ‐methyl‐5‐HT (5‐HT 2A+2B+2C ), MK212 (5‐HT 2B+2C ), or methyl‐chlorophenyl‐piperazine (5‐HT 2A+2C ) dose‐dependently stimulated ACTH secretion. The 5‐HT 3 agonist 2‐methyl‐5‐HT had no effect. Administration of a 5‐HT 1 agonist in combination with any of the 5‐HT 2 agonists DOI, S‐ α ‐methyl‐5‐HT or MK212 had an additive effect on the plasma concentration of ACTH. The ACTH stimulating effect of each of the 5‐HT agonists was inhibited 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‐HT 1A+2A+2C+5A+7 antagonist methysergide, the 5‐HT 2A antagonist ketanserine and the 5‐HT 2C+2A antagonist LY 53857. The 5‐HT 1A antagonist WAY 100635 enhanced 5‐HT‐ and 5‐HTP/Flx‐induced ACTH secretion, suggesting a presynaptic 5‐HT 1A autoreceptor effect of the drug. The 5‐HT 3 antagonist ondansetrone had no effect on the either of the 5‐HT agonists. The 5‐HT 3+4 antagonist tropisetrone attenuated the effect of 5‐HTP/Flx, which may suggest a stimulation of ACTH secretion via 5‐HT 4 receptors. It is concluded that 5‐HT 1A , 5‐HT 2A+2C , and to a lesser extent 5‐HT 1B receptors, but not 5‐HT 3 receptors are involved in the effects of serotonin agonists on ACTH secretion. Furthermore, an involvement of the 5‐HT 5A and the 5‐HT 7 receptor is possible.