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.
Matsuda
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nakano
Y
Y
Kanda
T
T
Iwata
H
H
Baba
A
A
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001923:Brain Chemistry; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D005260:Female; D006066:Gonads / Q000502:physiology / Q000601:surgery*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D051379:Mice; D010052:Ovariectomy; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D012727:Sex Characteristics; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D014316:Tritium; D007980:Levodopa; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D003345:Corticosterone