Evidence that a serotonergic mechanism stimulates the secretion of pituitary beta-endorphin-like immunoreactivity in the rat.

A pharmacological approach was used to investigate serotonergic control of the secretion of pituitary beta-endorphin-like immunoreactivity (beta-END-LI) in the rat. The administration of 75 or 200 mg/kg L-tryptophan (ip, over 30 min) increased brain serotonin by 17% and 19%, respectively, and increased circulating beta-END-LI from 0.30 +/- .06 to 0.56 +/- 0.7 and 0.64 +/- 0.8 ng/ml, respectively. D,L,5-Hydroxytryptophan (30 mg/kg, ip, over 30 min) produced a 4.9-fold increase in brain serotonin content and a 3.4-fold rise in plasma beta-END-LI. The administration of a serotonin reuptake blocker, fluoxetine (10 mg/kg, ip, over 15 min), elevated basal levels of plasma beta-END-LI from a control value of 0.38 +/- 0.02 to 1.21 +/- 0.32 ng/ml. Exposure to ether increased circulating beta-END-LI to 1.08 +/- 0.18 ng/ml, and fluoxetine treatment further increased this rise to 1.69 +/- 0.09 ng/ml (P less than 0.05). Quipazine, a serotonin receptor agonist, evoked a dose-related (2.5-5.0 mg/kg, ip) increase in circulating beta-END-LI levels by 15-45 min post injection. By contrast, intraventricular injection of the neurotoxin 5,7-dihydroxytryptamine (75 microgram free base, for 10 days) caused a 77% depletion of brain serotonin and attenuated the rise in beta-END-LI levels in response to immobilization (3.28 +/- 0.20 vs. 1.83 +/- 0.25 ng/ml). A higher dose of 5,7-dihydroxytryptamine (200 microgram free base, for 10 days) significantly decreased resting levels of beta-END-LI from 0.65 +/- 0.14 to 0.36 +/- 0.08 ng/ml. We conclude that brain serotonin neurons exert a stimulatory influence over the basal secretion of pituitary beta-END-LI and mediate, in part, the stress-induced release of this hormone.