Serotonergic mechanism in the control of beta-endorphin and ACTH release in male rats

The role of the serotonergic mechanism in the regulation of beta-endorphin (beta-EP and adrenocorticotropin (ACTH)-like immunoreactivity in plasma was investigated. Increases in beta-EP and ACTH-LI produced by quipazine maleate (QPZ), a serotonergic agonist, 1 hr after injection could be completely prevented by the serotonin (5-HT) antagonist, cinanserin (CIN), which when injected alone, decreased basal plasma concentrations of both beta-EP-LI and ACTH-LI. Concurrent injections of L-5-HTP with the 5-HT reuptake inhibitor, fluoxetine, produced an additive increase in plasma beta-EP-LI 1 hr after injection. Injection of the 5-HT antagonist, cyproheptadine, significantly decreased plasma beta-EP-LI. Stress by immobilization for 30 min or exposing the rats to 40 degree +/- 1 degree C for 30 min produced an approximate 4-fold increase in plasma beta-EP-LI and ACTH-LI, which was potentiated by I.P. injections of fluoxetine. Furthermore, the stress induced increases in plasma concentrations of beta-EP-LI and ACTH-LI were significantly reduced by the serotonin antagonists metergoline and cinanserin. These results suggest that 5-HT is a potent stimulator of both beta-EP and ACTH release and the increase in plasma concentrations of ACTH and beta-EP induced by stress are probably mediated, at least in part, by central serotonergic mechanisms.