SNRP Program at UCC

描述（由申请人提供）：UCC的SNRP-1计划围绕三个研究主题：去甲肾上腺素对可卡因致敏的调节，尼古丁和烟草西松烷类化合物的神经保护作用，以及西松烷类化合物对烟碱受体的作用机制。 天然产品核心提供烟草和海洋西松烷类化合物，包括已知的和新的。 每个项目都是与来自研究密集型机构的合作者合作进行的：加州大学洛杉矶分校，康奈尔大学。 （Ithaca）和Vollum研究所（OHSU）。 SNRP-1自1999年10月以来得到资助。 在第三年，向NIH提交了四份RO 1提案，其中三份正在重新提交过程中。 在同行评审期刊上发表了39篇手稿。 在报告的科学发现中，我们想提到以下几点：1）通过α-2受体的去甲肾上腺素能传递介导了可卡因在前额皮质的一些抑制作用。2)尼古丁和烟草西松烷类化合物都能保护海马脑片免受NMDA诱导的兴奋性毒性，但信号转导途径不同。3)西松烷类化合物是烟碱拮抗剂，其抑制作用可由某些可卡因衍生物释放。我们现在建议在第二个五年周期继续实施这一成功的方案。 三位新的科学家将解决亨廷顿病中的氧化损伤问题，甲状腺激素对nAChR和突触重塑的直接影响，以及精胺对钾通道的调节。 合作者来自华盛顿大学和加州大学洛杉矶分校。 计划活动包括研讨会，课程，旅行等，从SNRP-1到RO 1资金的过渡计划，建议目前的调查。 还提出了一项计划，以吸引波多黎各博士博士后与SNRP科学家在UCC的位置。

DESCRIPTION (provided by applicant): The SNRP-1 Program at UCC is centered around three research topics: norepinephrine modulation of sensitization to cocaine, neuroprotection by nicotine and tobacco cembranoids, and cembranoid mechanism of action on nicotinic receptors. A Natural Products Core provides tobacco and marine cembranoids, both known and new. Each project is performed in collaboration with a collaborator from a research-intensive institution: UCLA, Cornell U. (Ithaca) and the Vollum Institute (OHSU). SNRP-1 was funded since October 1999. Four RO1 proposals were presented to the NIH during the third year, three of which are now in the process of re-submission. Thirty nine manuscripts were published in peer-reviewed journals. Among the scientific discoveries reported, we would like to mention the following: 1) Noradrenergic transmission through alpha-2 receptors mediates some of the inhibitory effects of cocaine in the prefrontal cortex. 2) Both nicotine and tobacco cembranoids protect the hippocampal slice from NMDA-induced excitotoxicity, but the signal transduction pathways are different. 3) Cembranoids are nicotinic antagonists whose inhibitory action can be released by certain cocaine derivatives. We now propose to continue this successful program for a second cycle of five years. Three new scientists will address the issues of oxidative damage in Huntington disease, direct effects of thyroid hormones on the nAChR and on synapse remodelling, and modulation of potassium channels by spermine. Collaborators are from Washington University and UCLA. Program activities include seminars, courses, travel, etc. A transition plan from SNRP-1 to RO1 funding, is proposed for the present investigators. A plan to attract Puerto Rican Ph.Ds to postdoctoral positions with SNRP scientists at UCC is also presented.