Gender and estrous cycle effects of the 5-HT1A agonist, 8-OH-DPAT, on hypothalamic serotonin

Effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.04, 0.25, or 1.0 mg/kg), on hypothalamic serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and their ratio were determined in adult male rats and in diestrous, proestrous, and estrous female rats. Consistent with its action at the somatodendritic 5-HT1A autoreceptor, 8-OH-DPAT decreased the 5-HIAA/5-HT ratio, but the decrease was least evident in proestrous females and in males. Similar to hypothalamic tissue, there was also a decline in the 5-HIAA/5-HT ratio in the hippocampus after treatment with 0.25 mg/kg 8-OH-DPAT. When ovariectomized rats were treated with oil or estradiol benzoate followed 48 h later by oil or progesterone, 0.25 mg/kg 8-OH-DPAT produced a decrease in the hypothalamic 5-HIAA/5-HT ratio in every group except those rats treated with progesterone without estrogen priming. Treatment with estradiol benzoate increased hypothalamic 5-HIAA, and both progesterone and 8-OH-DPAT reduced the metabolite to the level of the ovariectomized control. These results suggest that both estrogen and progesterone contribute to an estrous cycle modulation of the 5-HT1A somatodendritic autoreceptor.