Remodeling of CNS Circuits--Early Oxytocin Exposure

本项目的目的是分析神经内分泌变化的中枢神经系统作为新生儿操作催产素（OT）的功能。来自行为和内分泌研究的初步数据表明，激素反应和行为的永久性变化，这是由于新生儿时期过量的OT或在此期间OT受体的阻断造成的。这些功能发现表明，这些功能的电路存在永久性改变的假设，这一假设将在两种动物模型：家鼠和草原田鼠。cFos的免疫反应性是细胞活化的非特异性标志物，将在神经系统（在某些情况下在肾脏）中测量，作为OT或选择性OT拮抗剂（OTA）新生儿治疗的函数。将给予不同剂量的OT或OTA。这些研究将进行，以验证OT操作的能力，影响组织激活，并建立最佳的程序，研究OT系统的新生儿操作的长期后果，作为更大的计划项目的一部分。将使用免疫组织化学在成年动物中进行额外的cFos研究：催产素（OT）、OT受体、精氨酸加压素（AVP）、AVP V1A受体和促肾上腺皮质激素释放激素（CrH）以及雌激素（E）和孕酮（P）受体。后一种措施将进行评估，例如，与项目II一起测试新生儿OT能够永久改变性腺类固醇敏感性的特定假设。

The purpose of this project is the analysis of neuroendocrine changes in the central nervous system as a function of neonatal manipulations of oxytocin (OT). Preliminary data from behavioral and endocrine studies suggest permanent changes in hormonal responses and in behavior, resulting from either excess OT during the neonatal period or blockade of OT receptors during this period. Such functional finding suggest the hypothesis that permanent alterations exists in the circuitry underlying these functions, this hypothesis will be examined in two animal models: domestic rats and prairie voles. Immunoreactivity for cFos, a non-specific marker for cellular activation, will be measured in the nervous system (and in some case in kidney) as a function of neonatal treatments with OT or a selective OT antagonist (OTA). Varying doses of either OT or OTA will be administered. These studies will be performed to verify the capacity of OT manipulations to influence tissue activation and to establish optimal procedures for studying the longer-term consequences of neonatal manipulations of the OT system-as part of the larger Program Project. Additional cFos studies will be conducted in adult animals using immunohistochemistry: Oxytocin (OT, OT receptors, Arginine vasopressin (AVP), AVP V1A receptors, and corticotropin releasing hormone (CrH), and receptors for estrogen (E) and progesterone (P). The latter measures will be assessed, for example, in conjunction with Project II to test the specific hypotheses that neonatal OT is capable of permanently altering sensitivity to gonadal steroids.