The influence of raphe lesions, p-chlorophenylalanine, and ketanserin on the estrogen-induced afternoon prolactin surge.

Female Sprague-Dawley rats were ovariectomized and 2 weeks later injected sc with 100 micrograms polyestradiol phosphate, a long-acting estrogen, to induce the afternoon PRL surge. In one series of experiments, the dorsal raphe (DRN), median raphe (MRN), and median raphe-pontine (MRN-RPn) regions were lesioned using a radiofrequency lesion maker set at 56 degrees C for 1 min. Lesions were induced, and atrial catheters were implanted on the day of estrogen injection. Six days later, blood samples were obtained every 2 h from 1100-2100 h to monitor the afternoon PRL surge. The animals were killed, and the hypothalami were quickly frozen on dry ice and stored at -60 degrees C for determination of amine content using HPLC with electrochemical detection. The rest of the brain was fixed and sectioned to verify the location of brain lesions. Complete lesions of the DRN markedly attenuated the PRL surge (P less than 0.001) compared to the effect of sham or incomplete lesions. MRN lesions did not significantly alter the PRL surge; however, MRN lesions that included the RPn significantly (P less than 0.001) attenuated the afternoon PRL surge. Significant decreases in serotonin (5-HT) and 5-hydroxyindoleacetic acid concentrations were observed in the arcuate, ventromedial, suprachiasmatic, and medial preoptic nuclei of the hypothalamus, but not in the median eminence of the lesioned rats. DRN and MRN-RPn lesions decreased the 5-HT concentration in the ARC and MPN compared to sham lesion and DRN incomplete lesion values. Other hypothalamic areas did not show a similar effect of the lesions. The concentrations of norepinephrine, dopamine, or dihydroxyphenylacetic acid were not altered by the lesions. In a second series of experiments one group of animals was injected ip with 10 mg/kg ketanserin, a serotonergic antagonist, at 1200 h on the sampling day. A second group was given 250 mg/kg p-chlorophenylalanine (PCPA) at 1700 h for 2 days before blood sampling was initiated on the third day. Both ketanserin and PCPA completely blocked the PRL surge. In the PCPA-injected animals, the 1100 and 1300 h PRL values were significantly higher (P less than 0.01) than those in vehicle-injected controls. Animals injected with ketanserin at 1200 h had a 1300 h PRL value significantly higher (P less than 0.01) than was observed in vehicle-injected animals.(ABSTRACT TRUNCATED AT 400 WORDS)