Amphetamine-mediated CREB phosphorylation & gene express

描述：（申请人摘要） 这是一个NIDA指导研究职业奖（KO 1）的要求，以研究 候选人对L-型Ca 2+通道在 安非他明介导的CREB磷酸化和强啡肽基因表达。 药物滥用研究的大部分进展都集中在神经和 滥用药物的行为药理学然而，直到最近， 与慢性药物使用相关的分子变化的重要性是 被解开了为了更好地了解成瘾性的性质， 这些药物，候选人将应用她的分子生物学背景来研究 成瘾行为背后的分子机制作为一名研究员， 候选人已经获得了知识，并接受了分子培训， 初级纹状体多巴胺信号转导通路的机制 cultures.体外研究表明多巴胺介导的CREB依赖性 磷酸化和L型钙通道的基因表达。这是高度 相关，因为最近L-型Ca 2+通道在 精神兴奋剂引起的行为通过这个奖项，候选人将 将体外观察到的分子事件与慢性炎症的体内模型相关联， 安非他明，在老鼠身上。L型钙通道在苯丙胺介导的神经细胞凋亡中的作用 将检查CREB磷酸化和强啡肽基因表达。两个CREB 和强啡肽直接参与了 精神兴奋剂可卡因候选人的培训主要是在 体外和细胞培养系统。通过这次获奖，她将进一步扩大她的 在体内工作的训练剧目。通过这次培训， 该奖项将包括学习神经解剖学，神经药理学和行为 滥用精神兴奋剂的影响。特别是，考生将学习（1） 脑切片中的原位杂交（2）立体定向手术引入 药物，反义寡核苷酸和病毒载体直接进入大脑， (3)病毒载体技术，一种强大的操纵神经元的新方法 功能，和（4）测试自发活动。

DESCRIPTION: (Applicant's Abstract) This is a request for a NIDA Mentored Research Career Award (KO1) to study the candidate's interest in the role of L-type Ca2+ channels in amphetamine-mediated CREB phosphorylation and dynorphin gene expression. Much of the progress in substance abuse research has focused on the neuro- and behavioral pharmacology of drugs of abuse. However only recently the significance of the molecular changes associated with chronic drug use are being unraveled. Towards a better understanding of the addictive properties of these drugs, the candidate will apply her molecular biology background to study the molecular mechanisms underlying addictive behavior. As a research fellow, the candidate has gained knowledge and received training in the molecular mechanism of the dopamine signal transduction pathway in primary striatal cultures. The in vitro studies indicate a dependence of dopamine-mediated CREB phosphorylation and gene expression on L-type Ca2+ channels. This is highly relevant because of the recent implication of L-type Ca2+ channels in psychostimulant-induced behavior. Through this award the candidate will correlate the molecular events observed in vitro to an in vivo model of chronic amphetamine, in rats. The role of L-type Ca2+ channels in amphetamine-mediated CREB phosphorylation and dynorphin gene expression will be examined. Both CREB and dynorphin have been directly implicated in the addictive properties of the psychostimulant, cocaine. The candidate's training has primarily been in in vitro and cell cultures systems. Through this award she will further expand her repertoire of training to in vivo work. The training received through this award will include learning the neuroanatomy, neuropharmacology and behavioral effects of psychostimulant abuse. In particular the candidate will learn (1) in situ hybridization in brain slices (2) stereotaxic surgeries to introduce drugs, antisense oligonucleotides and viral vectors directly into the brain, (3) viral vector technology, a powerful new method to manipulate neuronal function, and (4) test locomotor activity.