Effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor release from the rat hypothalamus in vitro

We investigated the effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor (CRF) release from the rat hypothalamus, and the effect of cyproheptadine on CRF-induced adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary (AP) in vitro using a perifusion system for rat hypothalami and AP, and a rat CRF radioimmunoassay. Cyproheptadine, 10⁻⁸ M, had a direct inhibitory effect on both basal and 10⁻⁹ M CRF-induced ACTH secretion from the rat AP in vitro. In addition, 10⁻⁹−10⁻⁷ M cyproheptadine inhibited basal CRF release in a dose-dependent fashion, and also suppressed serotonin- and KCl-induced CRF release. Conversely, 10⁻⁹−10⁻⁷ M reserpine failed to influence CRF release from the rat hypothalamus. These results indicate that a serotonergic mechanism may be involved in the CRF-releasing mechanism, and inhibition of depolarization-dependent calcium entry into cells and/or nerve endings. In addition an anti-serotonergic mechanism is involved in the inhibitory action of cyproheptadine.