Estrogen-induced sexual incentive motivation, proceptivity and receptivity depend on a functional estrogen receptor alpha in the ventromedial nucleus of the hypothalamus but not in the amygdala.

The display of copulatory behaviors usually requires the presence of a mate and is, therefore, preceded by a search for and approach to a potential partner. The intensity of approach behaviors is determined by a process labeled sexual incentive motivation. Although it is known that female sexual motivation depends on estrogens, their site of action within the brain is unknown. In the present experiment, we obtained data relevant to this issue. An shRNA encoded within an adeno-associated viral (AAV) vector directed against the estrogen receptor alpha (ERalpha) gene (or containing a nonsense base sequence as a control treatment) was injected bilaterally into the ventromedial nucleus of the hypothalamus (VMN) or the posterodorsal amygdala (MePDA) of female rats. After an 80% reduction of the number of ERalpha in the VMN, sexual incentive motivation was absent after treatment with estradiol and progesterone. Proceptivity and receptivity were also much reduced, while the number of rejections was enhanced. Suppression of the ERalpha in the MePDA lacked these effects. Likewise, the inactive control AAV vector failed to modify any behavior. Thus, the ERalpha in the VMN, but not in the MePDA, is important for proceptivity and receptivity as well as for sexual incentive motivation. These results show that ERalpha in the VMN is crucial for the entire sequence of behavioral events from the processes leading to the establishment of sexual contact until the accomplishment of copulatory behaviors.

The role of the estrogen receptor α in the medial preoptic area in sexual incentive motivation, proceptivity and receptivity, anxiety, and wheel running in female rats.

Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor α (ERα) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they were tested in the light/dark choice procedure, and after another 2 weeks they were subjected to a test in a brightly lit open field. Finally, the females were given free access to a running wheel for 88h. The females were treated with estradiol benzoate (EB), 18 or 1.5µg/kg, in randomized order 52h before each test except the running wheel. In that experiment, they were given EB 48h after introduction into the wheel cage. They were given progesterone, 1mg/rat, about 4h before all tests, except the running wheel. The shRNA reduced the number of ERα with 83%. Females with few ERα in the MPOA showed increased lordosis quotient after the 1.5µg/kg dose of EB. There was no effect on proceptive behaviors or on rejections. When given the 18µg/kg EB dose, there was no difference between females with few preoptic ERα and controls. In the test for sexual incentive motivation, females with few preoptic ERα approached the castrated male incentive more than controls, regardless of EB dose. They also moved a shorter distance. In the light/dark choice test as well as in the open field, females with few ERα in the MPOA showed signs of reduced fear/anxiety, since they spent more time in the light part of the dark/light box and in the center of the open field. Finally, the data from the running wheel showed that females with few preoptic ERα failed to show enhanced activity after treatment with EB. These data show that the preoptic ERα inhibits lordosis in females with an intermediate level of receptivity while it fails to do so in fully receptive females. The ERα in the MPOA seems to be necessary for selective approach to a sexual incentive. Finally, activation of this receptor appears to have anxiogenic effects in the procedures employed here. A hypothesis for how all these actions of the preoptic ERα contributes to efficient reproductive behavior is outlined.

The role of the estrogen receptor alpha in the medial amygdala and ventromedial nucleus of the hypothalamus in social recognition, anxiety and aggression.

Social recognition manifests itself in decreased investigation of a previously encountered individual. Estrogen receptor alpha (ERalpha) knock out mice show deficient social recognition and anxiety. These data show that the ERalpha is involved in these effects, but they do not say anything about the brain sites important for these effects. In this study, an shRNA encoded within an AAV viral vector directed against the ERalpha receptor gene (or containing luciferase control), was injected bilaterally into the posterodorsal amygdala (MePDA) or the ventromedial nucleus of the hypothalamus (VMN) of female rats. An 81% reduction of ERalpha expression in the MePDA eliminated social recognition. Moreover, this diminution of ERalpha in the MePDA reduced anxiety in the light/dark choice test. In contrast, social recognition was unaffected after ERalpha knockdown in the VMN while aggressiveness against the juvenile was enhanced. In conclusion, social recognition and anxiety in female rats are modulated by the ERalpha in the amygdala. Moreover, aggression against juveniles but not against adults could, at least partly, depend on the ERalpha in the VMN.

Ovarian hormones modulate social recognition in female rats.

The effects of estradiol and progesterone on social recognition were evaluated in a habituation-dishabituation procedure. Ovariectomized female rats were either given 18 microg/kg of estradiol benzoate followed by progesterone, 1 mg/rat, 48 h later or oil. The test consisted of 4 consecutive exposures to a juvenile rat and a final exposure to a novel juvenile. Although the time spent investigating the juvenile was reduced after repeated exposure in both groups, the reduction was larger in the group treated with ovarian hormones. When exposed to a novel juvenile, both groups displayed enhanced investigation. When the within-exposure investigation time was analyzed, a gradual reduction from the first to the last minute of the 5 min exposure was found in both groups. The reduction was faster in the group treated with estradiol+progesterone. There was no hormone effect on any other behavior pattern in the social recognition test. The hormone treatment produced a high level of receptive and proceptive behaviors according to a test for copulatory behavior performed immediately after the test for social recognition. These data show that ovarian hormones are not necessary for social recognition to occur, but they have a facilitatory effect. It is suggested that the contradictory findings reported in the literature can be explained by the fact that these hormones have rather subtle effects, perhaps detectable with the habituation-dishabituation procedure but not with the social discrimination procedure employed in most earlier studies.