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展开：去甲肾上腺素对可卡因的增敏作用、尼古丁和烟草西膜类化合物的神经保护作用以及西膜类化合物对尼古丁受体的作用机制。A Natural Products Core提供已知的和新的烟草和海洋西卜林化合物。每个项目都是与来自研究密集型机构的合作者合作完成的：加州大学洛杉矶分校、康奈尔大学(Ithaca)和Vollum Institute(OHSU)。SNRP-1是自1999年10月以来资助的。在第三年，向国家卫生研究院提交了四份RO1提案，其中三份正在重新提交。39篇手稿发表在同行评议的期刊上。在已报道的科学发现中，我们想提到以下几点：1)去甲肾上腺素能通过α-2受体传递，介导可卡因在前额叶皮质的一些抑制作用。2)尼古丁和烟草西膜醇对NMDA诱导的海马片兴奋性损伤均有保护作用，但信号转导途径不同。3)西膜类化合物是烟碱拮抗剂，其抑制作用可被某些可卡因衍生物释放。我们现在建议将这一成功的计划继续进行第二个周期，每五年一次。三位新科学家将解决亨廷顿病的氧化损伤问题，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制。合作者来自华盛顿大学和加州大学洛杉矶分校。方案活动包括研讨会、课程、旅行等。为目前的研究人员提出了从SNRP-1资金到RO1资金的过渡计划。还提出了一项计划，以吸引波多黎各博士在UCC的SNRP科学家的博士后职位。

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.