Role of serotonin in nocturnal and diurnal surges of prolactin in the pregnant rat.Endocrinology. 1989 Dec; 125(6):2875-80.E
Two surges of PRL designated as nocturnal (N) and diurnal (D) are observed during early pregnancy. The present study was undertaken to determine the involvement of serotonin (5-HT) in regulating these PRL surges. On day 7 of pregnancy intracarotid catheters were implanted, and blood samples were obtained at 0200 and 0400 h on day 8 and between midnight and 0600 h on day 9 to monitor the N surge. Rats were killed by decapitation, brains were quickly removed, frozen on dry ice, and stored at -70 C until later determination of indole and catecholamines. Pretreatment 24 h earlier with para-chlorophenylalanine (PCPA; 250 mg/kg BW), an inhibitor of 5-HT biosynthesis, did not affect the N PRL surge, although the hypothalamic concentrations of 5-HT and its metabolite 5-hydroxyindole acetic acid were greatly reduced. On the other hand, administration at 2400 h of ketanserin (KET; 10 mg/kg BW, ip) or LY-53857 (5 mg/kg BW, ip), two selective 5-HT2 antagonists, significantly (P less than 0.025 for KET and P less than 0.01 for LY-53857) reduced the N PRL surge. Neither KET nor LY-53857 altered the hypothalamic content of biogenic amines compared to that in saline-treated controls. Intravenous treatment with LY-53857 (1 mg/kg) at 0200 h after the onset of the N surge induced no change in plasma PRL levels compared to those in controls. To test whether 5-HT plays a role in the D surge, rats were decapitated at 1800 h after drug injection. Pretreatment with the same dose of PCPA (24 h), KET (2 h), or LY-53857 (2 h) that was given to rats in the N surge study significantly (P less than 0.01) reduced plasma PRL levels. As observed in the N study, PCPA greatly diminished the hypothalamic content of 5-HT and 5-hydroxyindole acetic acid, and also reduced dopamine, but to a much lesser extent than 5-HT. It is concluded that 5-HT contributes significantly to the generation of the D surge. Its role during the N surge remains uncertain due to the contradictory effects of the synthesis inhibitor PCPA and the receptor antagonists KET and LY-53857.