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Therapeutic plasticity: a novel paradigm for treating addiction

治疗可塑性：治疗成瘾的新范例

基本信息

批准号：
8352580
负责人：
Ilana Witten
金额：
$ 241.5万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2017-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (Provided by the applicant) Abstract: Despite the debilitating nature of addiction, and its associated societal and economic cost, there is currently no effective treatment. Here we propose to develop a bold new approach to the rampant neural plasticity induced by drugs of abuse. Although drug-induced plasticity is thought to be at the heart of the disease, it has not been possible to design circuit- level therapies to counteract these plastic changes because of technological limitations. My lab is now uniquely positioned to finally innovate such an approach, because of our expertise in both counteract the new field of optogenetics (the optical control of neural activity) and the emerging analysis of circuit-level mechanisms underlying addiction. To create this new approach to counteract addiction-related behavior, we will develop a novel panel of next-generation technologies togenetically and functionally target selected cell-types in rats. In order to counteract drug-induced plasticity, we will apply the new targeting technologies to activate the aversion and extinction in synchrony with the circuits that encode the drug experience, thereby circuits involved in weakening the drug-related associations and alleviating addiction-related behavior. Thus, we present here both a powerful new concept for the treatment of addiction, as well as the development of enabling technologies to achieve this vision. Public Health Relevance: Addiction is a devastating illness which destroys the lives of millions of people in the United States, is associated with enormous economic and societal cost, and is virtually without treatment. By developing a panel of new technologies designed to control neural activity in the appropriate cell-types in a rodent model of addiction, we open the door to the development of an exciting new approach to counteract drug-induced plasticity and addiction-related behavior.

描述（由申请人提供）翻译后摘要：尽管成瘾的衰弱的性质，其相关的社会和经济成本，目前还没有有效的治疗。在这里，我们提出了一个大胆的新方法，猖獗的神经可塑性引起的药物滥用。尽管药物诱导的可塑性被认为是疾病的核心，但由于技术限制，还不可能设计回路水平的疗法来抵消这些可塑性变化。我的实验室现在处于独特的位置，最终创新了这样一种方法，因为我们在抵消光遗传学（神经活动的光学控制）的新领域和对成瘾的电路水平机制的新兴分析方面都有专业知识。为了创造这种对抗成瘾相关行为的新方法，我们将开发一组新的下一代技术，以遗传学和功能性靶向大鼠中选定的细胞类型。为了对抗药物诱导的可塑性，我们将应用新的靶向技术来激活与编码药物体验的回路同步的厌恶和灭绝，从而参与削弱药物相关协会和减轻成瘾相关行为的回路。因此，我们在这里提出了一个强大的治疗成瘾的新概念，以及实现这一愿景的使能技术的发展。公共卫生相关性：成瘾是一种毁灭性的疾病，它摧毁了美国数百万人的生命，与巨大的经济和社会成本有关，并且几乎没有治疗。通过开发一组旨在控制啮齿动物成瘾模型中适当细胞类型的神经活动的新技术，我们为开发一种令人兴奋的新方法来对抗药物诱导的可塑性和成瘾相关行为打开了大门。