Oxytocin, Postnatal Experience & Adult Maternal Behavior

描述(申请人提供)：人类和非人类灵长类动物，数十年 的临床和研究结果清楚地表明，在 婴儿期和儿童期影响父母的素质和其他社会因素 成年后的行为以及应对压力的能力。近期 对大鼠早期母体分离效应的研究表明，出生后 养育也塑造了成年人的社会行为和压力反应 哺乳动物。这个啮齿动物模型允许更详细地研究 这些早期经验的终生后果背后的机制比现在 在灵长类动物身上可行。 在初步研究中，大鼠水坝经历了短暂和漫长的每日母体 婴儿时期的分离(BMS与LMS)分别表现为增加和 幼犬修饰(PG)减少、母体攻击和哺乳相关 焦虑程度下降。这些行为差异与对比有关 BMS和LMS程序对母婴护理坝数量的影响 从他们的母亲那里收到的。母亲们每天都要经历短暂而漫长的一天 幼崽分离分别表现为PG和Pg增加和减少 拱背护理(ABN)。 初步研究和其他最新证据表明，中枢催产素 (OT)通过对比调节不同大鼠水坝之间的行为 出生后多发性硬化症的经历和这些早期经历与 OT在发挥这些作用的脑部位的OT受体的显著差异 对行为的影响。这些发现表明多发性硬化症的影响模型如下 母亲和她们的雌性后代。中枢催产素促进哺乳期大鼠母亲 PG和ABN。每天短暂和长时间的幼犬分离(BMS和LMS程序) 增减分别提高和降低母亲的PG和ABN 这些母性行为的中枢OT增强。大坝的PG和ABN 频率随后决定了OT对行为的调节程度， 在雌性后代中发育，这会影响它们的成年PG和ABN 攻击性和焦虑的频率以及与哺乳相关的变化 行为。 拟议的实验将通过追求五个具体目标来测试该模型。 具体目标1是更详细地检查出生后 母性行为、攻击性、哺乳期变化与母体和母体的关系 焦虑和中枢OT受体结合。具体目标2、4和5是 确定PG的中枢OT调节程度是否存在差异， ABN、母亲的攻击性和焦虑导致了这些方面的不同程度 产后BMS与LMS经历的母亲之间的行为。大脑中的站点 谁的OT刺激PG和ABN也将被寻找。目标3是确定 短暂性睡眠障碍母亲PG-ABN的上升和下降 每天长时间的幼犬分离分别是增加和 减少OT对这些行为的增强。

DESCRIPTION (provided by applicant): In human and non-human primates, decades of clinical and research findings clearly show that nurturing received during infancy and childhood influences the quality of parental and other social behaviors as well as the ability to cope with stress during adulthood. Recent studies of early maternal separation effects in rats demonstrate that postnatal nurturing also shapes adult social behavior and stress responses in lower mammals. This rodent model permits more detailed investigation of the mechanisms underlying these life-long consequences of early experience than is feasible in primates. In Preliminary Studies, rat dams subjected to brief and long daily maternal separations (BMS vs. LMS) during infancy exhibited, respectively, increased and decreased pup-grooming (PG), maternal aggression and lactation-associated declines in anxiety. These behavioral differences were related to contrasting effects of the BMS and LMS procedures on the amount of maternal care dams received from their mothers. Mothers subjected to brief and long daily pup-separations exhibited respectively increased and decreased PG and arched-back nursing (ABN). Preliminary Studies and other recent evidence indicate that central oxytocin (OT) regulates behaviors that differ between rat dams with contrasting postnatal MS experience and these early experiences are associated with significant differences in OT receptors in brain sites where OT exerts these behavioral effects. These findings suggest the following model of MS effects on mothers and their female offspring. Central OT enhances lactating rat mothers' PG and ABN. Daily brief and long pup-separations (BMS and LMS procedures) respectively raise and lower mothers' PG and ABN by increasing and decreasing central OT enhancement of these maternal behaviors. Dams' PG and ABN frequencies subsequently determine the degree of OT regulation of behavior that develops in female offspring, which influences their adult PG and ABN frequencies as well as lactation-associated changes in aggression and anxious behavior. The proposed Experiments will test this model by pursuing five Specific Aims. Specific Aim 1 is to examine in more detail the relationships between postnatal BMS and LMS and dams' maternal behavior, aggression, lactation changes in anxiety and central OT receptor binding. Specific Aims 2, 4, and 5 are to determine whether differences in the degree of central OT regulation of PG, ABN, maternal aggression and anxiety contribute to contrasting levels of these behaviors between mothers with postnatal BMS vs. LMS experience. Brain sites in which OT stimulates PG and ABN will also be sought. Aim 3 is to determine whether upswings and downswings in PG-ABN in mothers subjected to brief and long daily pup-separations are the respective results of increased and decreased OT enhancement of these behaviors.