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 ovariecto mized rats on the lordosis-inhibiting action of the 5-HT1A agonist, 8- hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), were examined. In th e first week of hormonal priming, when rats were injected with estradi ol benzoate (2.5-50 mu g) plus 500 mu g progesterone, all groups were inhibited by intraperitoneal (i.p.) treatment with 0.15 mg/kg 8-OH-DPA T. However, in the second week of hormone treatment, the effects of 8- OH-DPAT on lordosis behavior were dose-dependently attenuated by estra diol benzoate. Such attenuation was present when animals were treated with estradiol benzoate on the day of ovariectomy and when the first e stradiol benzoate treatment was delayed for 2 weeks after ovariectomy. At least 3 days after the first injection with estradiol benzoate wer e required before the inhibitory effects of i.p. treatment with 8-OH-D PAT 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 in fused 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 i nterpreted as evidence that (1) estradiol benzoate's attenuation of th e effects of 8-OH-DPAT on lordosis behavior is both dose and time depe ndent; (2) 5-HT1A receptor action in the VMN is attenuated by the horm one treatment; and (3) female gonadal hormones reduce the potency of t he 5-HT1A agonist, 8-OH-DPAT, in inhibiting lordosis behavior. (C) 199 6 Academic Press, Inc.