Variance in sibling mothering received and adult mothering, anxiety and serotonin

描述（由申请人提供）：兄弟姐妹所接受的母爱和成人母爱、焦虑和血清素的差异 该 NRSA 提案的长期目标是确定兄弟姐妹之间接受母性护理的差异如何影响与后来兄弟姐妹差异相关的机制：1）母性行为，2）类焦虑行为，3）血清素合成 并释放。这项研究新颖且重要，因为众所周知，在人类和非人类动物中，家庭之间所接受的孕产妇护理差异很大，并对后代的神经和社会发展产生巨大影响，但在家庭内检验这一现象的研究却很少。我将使用大鼠模型来研究产后早期母婴互动与成年母亲、焦虑相关行为以及姐妹之间的血清素活性之间的关系。在具体目标 1 中，我将对生命前十天所接受的母性护理进行细致的观察，并确定与低舔的姐妹相比，高舔的雌性是否为自己的后代提供更多的母性护理。在成年期间，这些雌性还将在高架十字迷宫（一种经过充分验证的啮齿动物类焦虑行为测量方法）上进行测试，以确定焦虑的差异是否与母性差异有关。在具体目标 2 中，我将使用蛋白质印迹法来测量中缝背侧色氨酸羟化酶 2（TPH2，负责大脑血清素合成的主要酶）的表达，并假设与低舔的姐妹相比，高舔的雌性中色氨酸羟化酶 2 的表达上调。最后，在具体目标 3 中，我将确定高舔女性的终纹腹侧床核 (BSTv) 中的血清素释放是否高于其低舔姐妹，该区域接收来自 DR 的密集血清素能投射，并与母性行为和焦虑相关。为了实现这一目标，我将使用体内微透析来测量产后姐妹与幼崽互动时 BSTv 中血清素的释放情况。在该目标的第二个实验中，我将确定是否可以通过对低舔姐妹施用 5-HT1a 受体激动剂氟辛克生来最大程度地减少姐妹之间母性差异。在本提案中，我的目的是澄清焦虑相关和母性行为个体差异的早期围产期预测因素，这将促进更好地理解导致女性患成年焦虑症风险的发育轨迹。

DESCRIPTION (provided by applicant): Variance in sibling mothering received and adult mothering, anxiety and serotonin The long-term objectives of this NRSA proposal are to identify how variance among siblings in maternal care received influences mechanisms related to later sibling differences in: 1) maternal behavior, 2) anxiety-like behaviors, and 3) serotonin synthesis and release. This research is novel and important because in humans and non-human animals, it is well-known that variance in maternal care received greatly differs between families and has tremendous effects on offspring neurological and social development, yet studies examining this phenomenon within families are scarce. Using a rat model, I will examine the association between mother- infant interactions during the early postnatal period and adult mothering, anxiety-related behaviors, and serotonin activity among sisters. In Specific Aim 1, I will conducted finely detailed observations of maternal care received during the first ten days of life and determine if high-licked females provide more maternal care to their own offspring compared to their low-licked sisters. During adulthood, these females will also be tested on the elevated plus maze (a well-validated measure of anxiety-like behavior in rodents) to determine if differences in anxiety are associated with their differences in mothering. In Specific Aim 2, I wil use Western Blots to measure expression of tryptophan hydroxylase 2 (TPH2, the major enzyme responsible for brain serotonin synthesis) in the dorsal raphe with the hypothesis that it is upregulated in high-licked females compared to their low-licked sisters. Finally, in Specific Aim 3, I will determine if serotonin release in the ventral bed nucleus of the stria terminalis (BSTv), an area receiving dense serotonergic projections from the DR and associated with maternal behavior and anxiety, is higher in high-licked females than their low-licked sisters. To accomplish this, I will use in vivo microdialysis to measure serotonin release in the BSTv in postpartum sisters while they interact with pups. In a second experiment in this Aim, I will determine if variability among sisters in mothering can be minimized by administration of the 5-HT1a receptor agonist, flesinoxan, to low-licked sisters. In this proposal, I aim to clarify early perinatal predictors of individual differences in anxiety-related and mothering behaviors, which will promote a better understanding of developmental trajectories leading women toward risk for adult anxiety disorders.