The sexual receptivity of female mice, shown as lordosis response, is mainly regulated by estradiol action on estrogen receptor alpha (ERα) and beta (ERβ), depending on the day of the estrous cycle. Previous studies revealed that ERα in the ventromedial nucleus of the hypothalamus (VMH) plays an essential role in the induction of lordosis on the day of estrus (Day 1). However, the mechanisms of the transition to nonreceptive states on the day after estrus (Day 2) are not completely understood. In the present study, we investigated the possible role of ERβ, which is highly expressed in the dorsal raphe nucleus (DRN), in lordosis expression. We found that ERβ-Cre female mice, which were ovariectomized and primed with estradiol and progesterone to mimic the estrous cycle, showed high levels of lordosis on Day 2 when ERβ-expressing DRN (DRN-ERβ⁺) neuronal activity was chemogenetically suppressed. This finding suggests that excitation of DRN-ERβ⁺ neurons is necessary for the decline of lordosis on Day 2. Fiber photometry recordings during female–male behavioral interactions revealed that DRN-ERβ⁺ neuronal activation in response to male intromission was significantly more prolonged on Day 2 compared with Day 1. Chemogenetic overstimulation of DRN-ERβ⁺ neurons induced c-Fos expression in brain areas known to be inhibitory for lordosis expression, even though they did not express anterogradely labeled fibers of DRN-ERβ⁺ cells. These findings collectively suggest that DRN-ERβ⁺ neuronal excitation serves as an inhibitory modulator and is responsible for the decline in receptivity during nonestrus phases.

雌性小鼠的性容受性反应，表现为前凸反应，主要受雌二醇对雌激素受体 α （ERα） 和 β （ERβ） 的作用调节，具体取决于发情周期的日期。先前的研究表明，下丘脑腹内侧核 （VMH） 中的 ERα 在发情当天（第 1 天）诱导前凸中起着至关重要的作用。然而，在发情后的第二天（第 2 天）过渡到非感受状态的机制尚不完全清楚。在本研究中，我们研究了在中缝背核 （DRN） 中高度表达的 ERβ 在前凸表达中的可能作用。我们发现 ERβ-Cre 雌性小鼠被卵巢切除并用雌二醇和孕激素引发以模拟发情周期，当表达 ERβ 的 DRN （DRN-ERβ ⁺ ） 神经元活性被化学遗传学抑制时，第 2 天表现出高水平的前凸。这一发现表明，DRN-ERβ ⁺ 神经元的兴奋对于第 2 天前凸的下降是必要的。女性-男性行为互动期间的纤维光度测量记录显示，与第 1 天相比，第 2 天响应男性内切的 DRN-ERβ ⁺ 神经元激活显着延长。DRN-ERβ ⁺ 神经元的化学遗传学过度刺激在已知抑制前凸表达的大脑区域诱导 c-Fos 表达，即使它们不表达顺行标记的 DRN-ERβ ⁺ 细胞纤维。这些发现共同表明 DRN-ERβ ⁺ 神经元兴奋是一种抑制性调节剂，是非发情期容受性下降的原因。