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 ACTH-like immunoreactivity [LI] in plasma was investigated. Increases in .beta.-EP and ACTH-LI produced by quipazine maleate (QPZ), a serotonergic agonist, 1 h 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 [L-5-hydroxytryptophan] with the 5-HT reuptake inhibitor, fluoxetine, produced an additive increase in plasma .beta.-EP-LI 1 h 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. The stress-induced increases in plasma concentrations of .beta.-EP-LI and ACTH-LI were significantly reduced by the serotonin antagonists metergoline and cinanserin. Evidently 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.