Therapeutic plasticity: a novel paradigm for treating addiction

描述(由申请人提供) 摘要：尽管成瘾具有使人虚弱的本质，以及相关的社会和经济代价，但目前还没有有效的治疗方法。在这里，我们建议开发一种大胆的新方法来处理滥用药物引起的猖獗的神经可塑性。尽管药物诱导的可塑性被认为是这种疾病的核心，但由于技术限制，还不可能设计出电路级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地位，最终可以创新这样的方法，因为我们在抵消光遗传学(神经活动的光学控制)新领域和新兴的成瘾潜在电路水平机制分析方面的专业知识。为了创造这种新的方法来对抗与成瘾相关的行为，我们将开发一组新的下一代技术，从遗传学和功能上针对大鼠的特定细胞类型。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厌恶和消退，使其与编码药物体验的回路同步，从而参与削弱与药物相关的联系和减轻与成瘾相关的行为。因此，我们在这里提出了一个治疗成瘾的强有力的新概念，以及为实现这一愿景而开发的使能技术。 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活，与巨大的经济和社会成本有关，而且几乎没有治疗方法。通过开发一组旨在控制成瘾啮齿动物模型中适当细胞类型的神经活动的新技术，我们打开了开发一种令人兴奋的新方法的大门，以对抗药物诱导的可塑性和成瘾相关行为。

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.