GENES CONTROLLING LORDOSIS BEHAVIOR

控制脊柱行为的基因

• 批准号: 2244604
• 负责人: Donald W. Pfaff
• 金额: $ 14.3万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2244604
• 关键词: antisense nucleic acid; behavioral genetics; estradiol; estrogens; female; gender difference; gene expression; genetic regulation; hormone inhibitor; hormone receptor; hormone regulation /control mechanism; hypothalamus; laboratory rat; neurochemistry; oxytocin; progesterone; sex behavior

DESCRIPTION: This is a renewal of a project in its ninth year. The goal of this research is to understand the basic working circuit for producing lordosis behavior. The PI's previous work has yielded valuable information on the neural circuitry involved in controlling lordosis. The current work will extend this to an analysis of the molecular mechanisms controlling this behavioral response. The PI will focus this research on the role of oxytocin in mediating the lordosis response because a) it is a behaviorally relevant gene, b) oxytocin is found in brain areas shown to be part of the lordosis circuitry, and b) the genes for both the peptide (oxytocin) and its receptor are known. There are essentially two specific aims. The first is to examine the effectiveness of blocking the oxytocin gene on lordosis and to characterize this effect. The second aim is to do basically the same thing for the oxytocin receptor gene. The PI has preliminary data which provide support for the rationale and feasibility of the proposed experiments. The PI has shown, for example, that the facilitatory effect of oxytocin on lordosis is situated in the VMN, a site containing oxytocin receptors. He has also demonstrated that the excitatory action of oxytocin is mediated via oxytocin receptors. Using antisense oligo's for the oxytocin receptor the PI has found that lordosis is blocked when females are given estradiol (but not estrogen followed by progesterone). Finally, to show that the antisense technology works, he provides data from his laboratory showing that antisense oligo s for PR s reduce lordosis, and that PRir is reduced in VMN.

描述：这是对项目第九年的续约。目标 这项研究的是了解 产生脊柱障碍行为。 PI的先前工作已经产生 有关控制的神经电路的宝贵信息 Lordosis。当前的工作将扩展到对 控制这种行为反应的分子机制。 PI会 将这项研究重点放在催产素在介导dordisis中的作用 响应是因为a）它是一种行为相关的基因，b）催产素是 发现在大脑区域被证明是Lordosis电路的一部分，b） 已知肽（催产素）及其受体的基因。 本质上有两个具体的目标。首先是检查 阻断戈尔毒素基因对脊柱的有效性和 表征这种效果。第二个目标是基本相同 催产素受体基因的东西。 PI具有初步数据，可为基本原理提供支持 提出的实验的可行性。 PI显示，例如 催产素对脊柱的促进作用位于 VMN，一个含有催产素受体的部位。他也证明了 催产素的兴奋作用是通过催产素介导的 受体。使用反义寡核苷作为催产素受体PI具有 发现当雌性给雌二醇给雌性时，脊柱虫被阻塞（但没有 雌激素随后是孕酮）。最后，表明反义 技术工作，他提供了来自实验室的数据，这表明 反义的寡素s减少脊柱降临，而prir降低了 VMN。