Potentiation of Luteinizing Hormone Release by Serotonin Agonists in Ovariectomized Steroid-Primed Rats*

Abstract

The effects of 5-hydroxytryptophan (5-HTP), a 5-hydroxytryptamine (5-HT) precursor, and quipazine, a 5-HT agonist, were tested on the afternoon surge of LH in estradiol benzoate-primed ovariectomized rats pretreated with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, or pchloroamphetamine (PCA), a serotonin neurotoxin. The LH surge was completely abolished 24 h after a single injection of PCPA (300 mg/kg, ip) and was restored by subsequent injection of 5-HTP (50 mg/kg, ip) at 1200 h. On the other hand, administration of 5-HTP to rats prelreated with PCPA 48–72 h earlier significantly increased the LH surge above that of saline-pretreated controls (P < 0.01). The potentiated LH surge was seen only on the first but not on the second day of bleeding despite continued injections of 5-HTP. The administration of six consecutive doses of synthetic gonadotropin-releasing hormone (50 ng/100 g BW, ip) on the first day of bleeding to induce large surges of LH did not prevent 5-HTP from potentiating the LH surge on the following day. PCA (5 mg/kg, ip) alone had no effect on the LH surge, but potentiated the stimulatory action of 5-HTP on the LH surge (P < 0.05). Again, the potentiated 5-HTP action was not seen when a second dose of 5-HTP was given on the following day. Quipazine alone at a dose of 5 mg/kg (ip) had no effect on the LH surge, but potentiated the LH surge (P < 0.05) in rats pretreated with PCPA or PCA. The failure of a second dose of 5-HTP to potentiate the LH surge in rats pretreated with PCPA is not believed to be due to the depletion of a releasable pool of pituitary LH but, rather, to an unknown mechanism exerted on the brain by the first dose of 5-HTP. In general, these results suggest that the serotonergic system involved in the phasic release of LH can develop hyperresponsiveness to 5-HT agonists 48 h after the depletion of 5-HT by PCPA or PCA treatment.