Serotonergic 5-HT2A/2C receptors are involved in prolactin secretion in hyperestrogenic rats

Serotonin (5-HT) has been shown to participate in prolactin secretion through a complex process resulting in both positive and negative effects. Estrogen has also been recognized as being involved in this serotonergic effect on prolactin release. Therefore, the aim of the present study was to assess whether estradiol modulates serotonergic involvement in prolactin secretion though 5-HT1A and/or 5-HT2A/2C receptors. Ovariectomized female Wistar rats, treated for 2 weeks with estrogen to induce a hyperprolactinemic status (hyperestrogenic rats) or with sunflower oil vehicle (hypoestrogenic rats), were injected daily with normal saline solution or 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), an 5-HT2A/2C receptor agonist, for 4 days. Other groups of ovariectomized animals received 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or pindolol, an agonist and antagonist of the 5-HT1A receptor respectively, on the last day of treatment with estrogen or vehicle. Prolactin levels were compared among groups in each experiment under the distinct drug treatments. MK-212 was found to increase prolactin concentrations both in hyper- and hypoestrogenic females compared to controls (p<0.05). In contrast, prolactin levels remained similar to those of controls both in hyperestrogenic animals treated with 8-OH-DPAT and pindolol and in hypoestrogenic rats administered the same treatments. In conclusion, our findings indicate the involvement of 5-HT2A/2C receptors on prolactin release through serotonergic pathways in female animals, especially in hyperestrogenic states.