Role of serotonin in nocturnal and diurnal surges of prolactin in the pregnant rat.

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.