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

Abstract

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.

Fig. 1

a Mean ± SEM number of ERα in the VMN and MePDA after bilateral infusion of an AAV-associated shRNA directed against the ERα gene (ERα shRNA in the figure; VMN, n = 9; MePDA, n = 13; cerebral cortex, n= 9) or a control shRNA (AAV control in the figure; VMN, n = 9; MePDA, n = 13) into these structures. The sites of injection are illustrated by the bars. b Number of ERα in structures adjacent to the infusion sites, the medial arcuate nucleus (ArcM) for the VMN and the posteroventral amygdala (MePV) for the MePDA. In addition, the number of ERα in the VMN of animals given an infusion into the cerebral cortex above the VMN is shown. ERα shRNA, the group of females injected by shRNA against the ERα gene either in the VMN or in the MePDA; AAV control, the group of females injected by inactive shRNA either in the VMN or in the MePDA; ERα shRNA cortex, the group of females injected by shRNA against the ERα gene in the cortex. ∗ p < 0.05 compared to ERα shRNA.

Fig. 2

Immunocytochemical staining of brain slices in the VMN and the MePDA. Only slices with the greatest ERα staining have been chosen. Scale bar is 200 μm. ArcM = Arcuate nucleus; MePV = medial posteroventral amygdala. Notice a reduction of ERα staining in the VMN and MePDA but not in the ArcM and MePV in animals infused with ERα shRNA compared to animals infused into the cortex and those infused with AAV control.

Fig. 3

Mean ± SEM of parameters of sexual incentive motivation in female rats with a reduced number of ERα in the VMN or MePDA and the corresponding controls. a Time (s) spent in the intact and castrated male incentive zones, respectively. b Preference score. Subjects treated with ERα shRNA in the VMN do not approach the sexual incentive more than the social incentive, while the same treatment in the MePDA fails to reduce sexual incentive motivation. ∗ Different from the time spent in the intact male zone, p < 0.05. ^x Different from no preference (a score of 0.5), p < 0.05. Lines indicate significant differences between groups: ⁺ p < 0.05. For further details, see legend to figure 1.

Fig. 4

a Lordosis quotient (LQ), b proceptive behaviors and c rejections in female rats with a reduced number of ERα in the VMN or MePDA and the corresponding controls. After a substantial reduction of ERα in the VMN, proceptivity and receptivity (lordosis) were reduced while rejections were enhanced. No effects were observed after a similar reduction of the ERα in the MePDA. Data are mean ± SEM. ∗ Different from ERα shRNA, p < 0.05. For further details, see legend to figure 1.