College of Biological Sciences and Engineering, North Minzu University, Yinchuan, Ningxia, China.
Behav Pharmacol. 2024 Oct 1;35(7):386-398. doi: 10.1097/FBP.0000000000000791. Epub 2024 Sep 11.
Increasing evidence indicates that prenatal cocaine exposure may result in many developmental and long-lasting neurological and behavioral effects. The behaviors of female animals are strongly associated with the estrous cycle. Estrogen receptors and oxytocin are important neuroendocrine factors that regulate social behavior and are of special relevance to females. However, whether prenatal cocaine exposure induces estrous cycle changes in offspring and whether neurobehavioral changes in estrus and diestrus offspring differ remains unclear. On gestational day 12, mice were administered cocaine once daily for seven consecutive days, then the estrous cycle was examined in adult female offspring, as well as locomotion, anxiety level, and social behaviors, and the expression of estrogen receptor alpha-immunoreactive and oxytocin-immunoreactive neurons were compared between estrus and diestrus offspring. Prenatal cocaine exposure resulted in the shortening of proestrus and estrus in the offspring. During estrus and diestrus, prenatally cocaine-exposed offspring showed increased anxiety levels and changed partial social behaviors; their motility showed no significant differences in estrus, but declined in diestrus. Prenatal cocaine exposure reduced estrogen receptor alpha-immunoreactive expression in the medial preoptic area, ventromedial hypothalamic nucleus, and arcuate nucleus and oxytocin-immunoreactive expression in the paraventricular nucleus in estrus and diestrus offspring. These results suggest that prenatal cocaine exposure induces changes in the offspring's estrous cycle and expression of estrogen receptor alpha and oxytocin in a brain region-specific manner and that prenatal cocaine exposure and the estrous cycle interactively change motility and partial social behavior. Estrogen receptor alpha and oxytocin signaling are likely to play important concerted roles in mediating the effects of prenatal cocaine exposure on the offspring.
越来越多的证据表明，产前可卡因暴露可能导致许多发育和持久的神经和行为影响。动物的行为与发情周期密切相关。雌激素受体和催产素是调节社会行为的重要神经内分泌因素，对女性尤为重要。然而，产前可卡因暴露是否会导致后代发情周期改变，以及发情和间情期后代的神经行为变化是否不同，目前尚不清楚。在妊娠第 12 天，每天给小鼠注射可卡因一次，连续 7 天，然后检查成年雌性后代的发情周期，以及运动、焦虑水平和社会行为，并比较发情和间情期后代雌激素受体α免疫反应和催产素免疫反应神经元的表达。产前可卡因暴露导致后代发情前期和发情期缩短。在发情期和间情期，产前可卡因暴露的后代表现出焦虑水平升高和部分社会行为改变；它们的运动能力在发情期没有显著差异，但在间情期下降。产前可卡因暴露降低了发情和间情期后代中中前脑区、腹内侧下丘脑核和弓状核中雌激素受体α免疫反应和室旁核中催产素免疫反应神经元的表达。这些结果表明，产前可卡因暴露以脑区特异性方式诱导后代发情周期和雌激素受体α和催产素表达的改变，产前可卡因暴露和发情周期以交互方式改变运动能力和部分社会行为。雌激素受体α和催产素信号可能在介导产前可卡因暴露对后代的影响方面发挥重要的协同作用。
