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）摘要：尽管成瘾具有使人衰弱的性质及其相关的社会和经济成本，但目前尚无有效的治疗方法。在这里，我们建议开发一种大胆的新方法来应对滥用药物引起的猖獗的神经可塑性。尽管药物引起的可塑性被认为是该疾病的核心，但由于技术限制，尚不可能设计出电路级疗法来抵消这些可塑性变化。我的实验室现在处于独特的地位，最终能够创新这种方法，因为我们在抵消光遗传学（神经活动的光学控制）新领域和对成瘾背后的电路级机制的新兴分析方面的专业知识。为了创造这种新方法来抵消与成瘾相关的行为，我们将开发一组新颖的下一代技术，从基因上和功能上针对大鼠中选定的细胞类型。为了抵消药物引起的可塑性，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消退，从而参与削弱与药物相关的关联并减轻与成瘾相关的行为的回路。因此，我们在这里提出了治疗成瘾的强大新概念，以及实现这一愿景的支持技术的开发。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，造成巨大的经济和社会成本，而且几乎无法治疗。通过开发一系列新技术，旨在控制成瘾啮齿动物模型中适当细胞类型的神经活动，我们为开发一种令人兴奋的新方法来抵消药物引起的可塑性和成瘾相关行为打开了大门。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dopamine neurons modulate neural encoding and expression of depression-related behaviour.

多巴胺神经元调节抑郁相关行为的神经编码和表达。

DOI：
发表时间：
2013-01-24
期刊：
影响因子：
64.8
作者：
Tye, Kay M;Mirzabekov, Julie J;Warden, Melissa R;Ferenczi, Emily A;Tsai, Hsing;Finkelstein, Joel;Kim, Sung;Adhikari, Avishek;Thompson, Kimberly R;Andalman, Aaron S;Gunaydin, Lisa A;Witten, Ilana B;Deisseroth, Karl
通讯作者：
Deisseroth, Karl

Dissociated sequential activity and stimulus encoding in the dorsomedial striatum during spatial working memory.

空间工作记忆期间背内侧纹状体中分离的顺序活动和刺激编码。

DOI：
发表时间：
2016-09-16
期刊：
影响因子：
7.7
作者：
Akhlaghpour, Hessameddin;Wiskerke, Joost;Choi, Jung Yoon;Taliaferro, Joshua P;Au, Jennifer;Witten, Ilana B
通讯作者：
Witten, Ilana B

Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.

将胆碱能中间神经元、突触可塑性和可卡因关联消失期间的行为联系起来。