Oxytocin, Postnatal Experience & Adult Maternal Behavior

描述（由申请人提供）：在人和非人灵长类动物中，数十年 的临床和研究结果清楚地表明， 婴儿期和儿童期影响父母和其他社会 行为以及应对压力的能力。最近 对大鼠早期母体分离效应的研究表明， 养育也塑造了成年人的社会行为和压力反应， 哺乳动物这种啮齿动物模型允许更详细地研究 这些早期经验的终身后果的潜在机制， 在灵长类动物中是可行的 在初步研究中，对大鼠母体进行短暂和长期的每日母体 在婴儿期的分离（BMS与LMS）分别表现出增加， 减少小狗梳理（PG），母亲的侵略和哺乳相关的 焦虑下降。这些行为差异与对比 BMS和LMS程序对孕产妇护理母鼠数量的影响 从母亲那里得到的。母亲们每天都要接受短暂和漫长的 幼仔分离分别表现出增加和减少的PG和 拱背式护理（ABN）。 初步研究和其他最近的证据表明，中枢催产素 (OT)调节行为不同的大鼠母鼠与对照 出生后的MS经历，这些早期经历与 在大脑中的OT受体的显着差异，其中OT发挥这些 行为效应这些发现表明以下MS影响 母亲和她们的雌性后代中枢OT增强哺乳期大鼠母亲的 PG和ABN。每日短期和长期幼仔分离（BMS和LMS程序） 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。母兽PG和ABN 频率随后决定OT调节行为的程度， 在雌性后代中发展，影响其成年PG和ABN 频率以及哺乳相关的变化，在侵略和焦虑 行为 拟议的实验将通过追求五个具体目标来测试这个模型。 具体目标1是更详细地检查产后 BMS和LMS与母鼠的母性行为、攻击性、泌乳变化 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调节程度的差异， ABN，母亲的侵略和焦虑有助于这些对比水平 产后BMS与LMS经验的母亲之间的行为。大脑部位 也将寻求OT刺激PG和ABN的方式。目标3：确定 是否在母亲的PG-ABN的上升和下降受到短暂和 长期的每日小狗分离是各自的结果增加， 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.