GENES CONTROLLING LORDOSIS BEHAVIOR

控制脊柱行为的基因

• 批准号: 2415883
• 负责人: Donald W. Pfaff
• 金额: $ 15.47万
• 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 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415883
• 关键词: antisense nucleic acid; behavioral /social science research tag; 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：这是该项目第九年的更新。目标 这项研究的目的是了解基本工作电路 产生脊柱前凸的行为。 PI 之前的工作已经取得成果 关于参与控制的神经回路的有价值的信息 脊柱前凸。当前的工作将扩展到对 控制这种行为反应的分子机制。 PI 将 这项研究的重点是催产素在调节脊柱前凸中的作用 反应，因为 a) 它是行为相关基因，b) 催产素是 在被证明是脊柱​​前凸回路一部分的大脑区域中发现，并且 b) 肽（催产素）及其受体的基因都是已知的。 本质上有两个具体目标。首先是检查 阻断催产素基因对脊柱前凸的有效性 描述这种效应的特征。第二个目标是做基本相同的事情 催产素受体基因的东西。 PI 拥有初步数据，可为基本原理提供支持 所提出的实验的可行性。例如，PI 已表明， 催产素对脊柱前凸的促进作用位于 VMN，一个含有催产素受体的位点。他还展示了 催产素的兴奋作用是通过催产素介导的 受体。使用反义寡核苷酸作为 PI 的催产素受体 发现当女性给予雌二醇时，脊柱前凸会被阻止（但不是 雌激素，其次是孕激素）。最后证明反义 技术有效，他提供了他实验室的数据表明 PR 的反义寡核苷酸可减少脊柱前凸，并且 PRir 在 虚拟网络。