Gonadectomy changes the pituitary-adrenocortical response in mice to 5-HT1A receptor agonists

The effects of 5-HT1A receptor agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), BP-554 and buspirone on the serum corticosterone level were significantly more pronounced in female than in male mice. A similar sex difference was observed for the effect of 8-OH-DPAT on the plasma ACTH level. Pretreatment with proadifen, an inhibitor of microsomal drug-metabolizing enzymes, did not affect the sex difference in the effect of 8-OH-DPAT. The corticosterone response to 8-OH-DPAT in female mice was attenuated by ovariectomy. The effect of 8-OH-DPAT in ovariectomized mice was enhanced by chronic estradiol and the enhancement was blocked by testosterone. In male mice the corticosterone response to 8-OH-DPAT increased at 5 weeks after castration but had not changed at 2 weeks. Chronic estradiol enhanced the corticosterone response to 8-OH-DPAT in castrated mice. There was no difference between sexes in [3H]8-OH-DPAT binding to membranes and in the contents of 5-HT and 5-hydroxyindoleacetic acid in the hypothalamus. Accumulation of 5-hydroxytryptophan after decarboxylase inhibition in the hypothalamus was however greater in female than in male mice.