Antagonism of sexual behavior in female rats by ventromedial hypothalamic implants of antiestrogen

The present experiments sought to identify brain regions in which implants of an antiestrogen would antagon-ize the ability of a systemic estradiol treatment to activate sexual behavior in female rats. In experiment I, ovariectomized female rats were implanted subcutaneously with 5-mm Silastic capsules containing a 5% concentration of estradiol and injected with 500 pg progesterone 2 days later, 4-5 h before testing for sexual behavior. Bilateral intracranial implants of 1% crystalline concentrations of the high-affinity antiestrogens monohydroxytamoxifen (TAM) or keoxifene placed into the ventromedial nucleus of the hypothalamus (VM) 24 h prior to estradiol treatment significantly reduced lordosis re-sponsivity compared with control females receiving empty cannulae. Implants of 1% TAM into the medial preoptic area or medial amygdala 24 h priorto estradiol hat no significant effect on lordosis. Similarly, implants of 1%TAM into the VM 12 h zz/irer estradiol had no effect on lordosis. In experiment 2, lordosis was activated by subcutaneous implants of Silastic capsules containing 1% estradiol plus 500 ug progesterone. In this experiment, implants of 1% TAM into the VM 24 h prior to estradiol significantly reduced lordosis only if both cannulae tips were in, or adjacent to, the VM. Females receiving intracranial 1% TAM. but whose cannulae (even unilaterally) were outside the VM. had levels of lordosis equivalent to those of control females. Increasing the concentration of intracranial TAM to 10% virtually eliminated lordosis in lemales with bilateral implants in the VM. whereas females receiving intracranial 10% TAM in the region of, but outside, the VM showed no evidence of a lordosis deficit. These results indicate that selectively blocking estradiol receptors in VM neurons can antagonize the effects of systemically delivered estradiol on lordosis. Taken together with previous data, these results suggest that stimulation of VM estrogen receptors is both necessary and sufficient for the hormonal activation of lordosis in rats.