Serotonin Agonists Cause Parallel Activation of the Sympathoadrenomedullary System and the Hypothalamo-Pituitary-Adrenocortical Axis in Conscious Rats

Abstract

The effects of three potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles on sympathoadrenomedullary and hypothalamo-pituitary- adrenocortical axis functions were assessed in conscious, freely moving male Sprague-Dawley rats. The 5-HTiA agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5- HT_1A agonist, m-chlorophenylpiperazine (m-CPP), and the 5- HT₂/5-HT_lc agonist, l-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI), all produced marked dose-dependent increases in plasma epinephrine and ACTH concentrations. Both epinephrine and ACTH responses peaked at 10 min and showed strong positive correlations across all drugs and doses studied. Corticosterone increases showed a saturable response pattern and were close to the maximum level with a relatively small (∼2.5-fold) increase in plasma ACTH concentrations. Norepinephrine levels showed small dose-dependent increases after 8- OH-DPAT and m-CPP and decreases after DOI treatment. These results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis can be activated via 5-HT₁ and 5-HT₂ receptors and that these two systems may have common or similar regulatory mechanisms triggered by these stimuli.