Prior treatment with estrogen attenuates the effects of the 5-HT1A agonist, 8-OH-DPAT, on lordosis behavior.

The effects of repeated treatment with estradiol benzoate to ovariectomized rats on the lordosis-inhibiting action of the 5-HT1A agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), were examined. In the first week of hormonal priming, when rats were injected with estradiol benzoate (2.5-50 micrograms) plus 500 micrograms progesterone, all groups were inhibited by intraperitoneal (i.p.) treatment with 0.15 mg/kg 8-OH-DPAT. However, in the second week of hormone treatment, the effects of 8-OH-DPAT on lordosis behavior were dose-dependently attenuated by estradiol benzoate. Such attenuation was present when animals were treated with estradiol benzoate on the day of ovariectomy and when the first estradiol benzoate treatment was delayed for 2 weeks after ovariectomy. At least 3 days after the first injection with estradiol benzoate were required before the inhibitory effects of i.p. treatment with 8-OH-DPAT were attenuated. Although the magnitude was reduced, higher doses of 8-OH-DPAT (0.4, 0.45, and 0.5 mg/kg) continued to inhibit lordosis behavior even after the second hormonal priming. When 8-OH-DPAT was infused directly into the ventromedial nucleus of the hypothalamus (VMN), the lordosis-inhibiting effects of 8-OH-DPAT were reduced as soon as 2 days after the first estradiol benzoate injection. These data are interpreted as evidence that (1) estradiol benzoate's attenuation of the effects of 8-OH-DPAT on lordosis behavior is both dose and time dependent; (2) 5-HT1A receptor action in the VMN is attenuated by the hormone treatment; and (3) female gonadal hormones reduce the potency of the 5-HT1A agonist, 8-OH-DPAT, in inhibiting lordosis behavior.