Estrogen and 5-HT(1A) receptor function

The effects of estrogen treatment on 5-HT1A receptor function were examined. When ovariectomized rats were given a single treatment with 25 μm estradiol benzoate followed 48 hr later with 500 μg progesterone, the 5-HT1A receptor agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), inhibited lordosis behavior. However, when rats were given a second estradiol benzoate injection (seven days later) followed by progesterone, the ability of 8-OH-DPAT to inhibit lordosis behavior was reduced. The reduction in the ability of 8-OH-DPAT to inhibit lordosis behavior lasted for at least 10 days, but after 15 days the inhibitory effects of 8-OH-DPAT on lordosis behavior had been restored. The protective effects of estrogen were also apparent when 17β-estradiol was infused into the ventromedial nucleus of the hypothalamus (VMN) seven days before the second treatment with systemic estradiol benzoate. Consistent with hormonal changes that occur during the estrous cycle, estradiol benzoate also reduced the effectiveness of 8-OH-DPAT in inhibiting lordosis behavior 48 hr after treatment. Although the mechanisms for the protection of estrogen against the effects of 8-OH-DPAT on lordosis behavior are unknown, rats coinfused with N6,2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate (dibutyryl cAMP) and 8-OH-DPAT showed less inhibition of lordosis behavior than rats infused with 8-OH-DPAT alone. These data are consistent with the suggestion that estrogen activates a neural “cascade” that leads to a reduction in functioning of 5-HT1A receptors.