Effects of manipulating serotonin on the incidence of ovulation in the rat

Previous studies have shown that while depletion of brain serotonin by the administration of p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, blocks the daily surge of LH in oestrogen-treated ovariectomized rats, restoration of serotonin synthesis by treatment with its immediate precursor, 5-hydroxytryptophan (5-HTP), at a critical time of day, reinstates the surge. The present study indicates that the experimental procedure involving serotonin depletion and its subsequent replenishment may also be used to control the preovulatory LH surge and ovulation in intact cyclic rats provided that (1) the PCPA is administered subcutaneously rather than intraperitoneally nad (2) the 5-HTP is given in conjunction with carbidopa, a peripheral decarboxylase inhibitor: the latter observation providing further evidence for a central role for serotonin in the control of ovulation. These precautions were unnecessary when oestrogen was administered at the same time as the PCPA. It appears that PCPA administered intraperitoneally results in a suppression of the preovulatory rise in oestrogen secretion (and may have additional deleterious effects at the level of the ovaries) and that 5-HTP, in the absence of supplementary oestrogen, may block ovulation by peripheral action after conversion to serotonin. This study indicates the need for caution when using pharmacological 'cocktails' to investigate neuroendocrine events underlying ovulation when the experiments are carried out in the presence of the ovaries.