Serotonergic 5-HT2A receptors important for the oestradiol-induced surge of luteinising hormone-releasing hormone in the rat

Serotonin (5-HT) plays a role in mediating the oestradiol-induced surge of luteinising hormone (LH), but so far the 5-HT receptor subtype involved has not been identified. Our previous in-situ hybridization and pharmacologica l studies suggest that the action of 5-HT involves the 5-HT2A receptor. The aim of the present study was to investigate this possibility by the direct approach of determining whether 5-HT2A receptor antagonists block the oest radiol-induced surge of luteinising hormone releasing hormone (LHRH). Adult female Wistar rats, which had shown at least two consecutive 4-day oestrou s cycles, were ovariectomised under halothane anaesthesia in the morning of dioestrus and injected with vehicle (arachis oil) alone or oestradiol benz oate (OB). At 12.00 h of the next day, presumptive pro-oestrus, the animals were injected intraperitoneally with one of three 5-HT2A antagonists, a se lective 5-HT reuptake inhibitor (fluoxetine), or the appropriate vehicles; hypophysial portal blood was then collected under alphaxalone anaesthesia b etween 15.00 and 19.00 h. The amount of LHRH released into hypophysial port al blood during consecutive 30-min periods was determined by radioimmunoass ay. As expected, oestradiol, but not oil, triggered a surge of LHRH in hypo physial portal blood with a peak at about 16.00 h of presumptive pro-oestru s. This oestradiol-induced surge of LHRH was blocked by ketanserin, ritanse rin and the highly selective 5-HT2A receptor antagonist, RP62203, but not b y fluoxetine. These results provide the first direct evidence that the 5-HT 2A receptor plays an important role in the oestradiol-induced surge of LHRH .