Serotonin (5-HT) stimulation of prolactin (PRL) secretion is mediated through the dopaminergic (DAergic) system, with 5-HT ligands having no direct effect on pituitary PRL release. Infusion of 5-HT into the third ventricle (ICV) or electrical stimulation (ES) of the medial preoptic area (POM) or the ventromedial nucleus (VMN) induces an increase in circulating PRL in the turkey. These increases in PRL do not occur when a selective antagonist blocks the D1 dopamine (DA) receptors in the infundibular area (INF). In this study, the ICV infusion of (R)(-)-DOI hydrochloride (DOI), a selective 5-HT2A eceptor agonist, caused PRL to increase. Pretreatment with Ketanserin tartrate salt (KETAN), a selective 5-HT2A receptor antagonist, blocked DOI-induced PRL secretion, attesting to the specificity of the response. DOI-induced PRL secretion was prevented when the D1 DA receptors in the INF were blocked by the D1 DA receptor antagonist, R(+)-SCH-23390 hydrochloride microinjection, suggesting that the DAergic activation of the vasoactive intestinal peptide (VIP)/PRL system is mediated by a stimulatory 5-HT2A receptor subtype. The DOI-induced PRL increase did not occur when (±)-8-OH-DPAT (DPAT) was concurrently infused. DPAT is a 5-T1A receptor agonist which appears to mediate the inhibitory influence of 5-HT on PRL secretion. When DPAT was microinjected directly into the VMN, it blocked the PRL release affected by ES in the POM. These data suggested that when 5-HT2A receptors are activated, they influence the release of DA to the INF. When 5-HT1A receptors are stimulated, they somehow inhibit the PRL-releasing actions of 5-HT2A receptors. This inhibition could take place centrally, or it could occur postsynaptically at the pituitary level. It is known that D2 DA receptors in the pituitary antagonize PRL-releasing effect of VIP. A release of DA to the pituitary, initiated by 5-HT1A receptors, could effectively inhibit PRL secretion.
Bibliographical noteFunding Information:
This work was supported by National Research Initiative Competitive Grants Nos. 2004-35203-14771 and 2007-35203-18072 from the USDA Cooperative State Research, Education and Extension Service. The Statistical Consulting Service at the University of Minnesota and in particular Dr. Aaron Rendahl helped with analysis of this study.
- Serotonin receptors subtypes