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：这是一个项目的第九个年头。目标 这项研究的目的是了解基本的工作电路， 产生脊柱前凸行为。私家侦探之前的工作 关于控制神经回路的有价值的信息 脊柱前凸目前的工作将扩展到分析 控制这种行为反应的分子机制。PI将 本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）它是一个行为相关的基因，B）催产素是 在显示为脊柱前凸回路的一部分的脑区域中发现，和B） 肽（催产素）及其受体的基因是已知的。 基本上有两个具体目标。第一，检查 阻断催产素基因对脊柱前凸的有效性， 描述这种效果。第二个目标是做基本相同的事情 催产素受体基因。 PI有初步数据，可为基本原理提供支持， 实验的可行性。例如，PI显示， 催产素对脊柱前凸的促进作用位于 VMN，含有催产素受体的部位。他还证明， 催产素的兴奋作用是通过催产素 受体。使用催产素受体的反义寡核苷酸，PI具有 研究发现，当女性服用雌二醇时，脊柱前凸被阻断（但不 雌激素，然后是孕酮）。最后，为了证明反义 他提供的实验室数据显示， PR的反义寡核苷酸减少了脊柱前凸，并且PRir在 VMN。