CB1 receptor in medium spiny neurons in amphetamine sensitization

描述(申请人提供)：毒瘾，包括苯丙胺及其衍生物，每年给美国造成约1810亿美元的损失。不幸的是，人们对药物寻找行为和成瘾的分子基础仍知之甚少，仍有许多有待研究的地方。因此，必须确定和测试针对药物成瘾的新的治疗方法，特别是苯丙胺。为了做到这一点，有必要更好地了解与这一现象有关的大脑区域和细胞类型。最近令人兴奋的研究表明，在成瘾相关行为中，一些行为表型是由CB1受体控制的。这些受体在GABA能中棘神经元(MSN)上高水平表达。NRSA的目的是更好地了解MSN上表达的CB1受体如何影响苯丙胺敏化和条件性位置偏爱后观察到的行为表型。这将通过在特定目标1中验证我们的病毒策略来实现，即通过直接或间接途径将CB1受体特异性地递送到MSN。在具体目标2中，将确定直接或间接MSN对苯丙胺敏化和条件性位置偏爱的贡献。此外，还将研究苯丙胺致敏的分子相关性。总之，这项研究的目的将直接评估MSN上的CB1受体如何对苯丙胺的行为反应做出贡献。

DESCRIPTION (provided by applicant): Drug addiction, including to amphetamines and their derivatives, cost the United States approximately $181 billion each year. Unfortunately, the molecular basis for drug seeking behaviors and addiction is still quite poorly understood and much remains to be studied. Therefore, novel therapeutic treatments for drug addiction, especially for amphetamines, must be identified and tested. In order to do this, a better understanding of the brain regions and cell types involved in this phenomenon is necessary. Recent exciting research has established that some behavioral phenotypes are controlled by the CB1 receptors in the context of addiction- related behaviors. These receptors are expressed at high levels on the GABAergic medium spiny neurons (MSNs). The goal of this NRSA is to better understand how the CB1 receptors expressed on MSNs contribute to the behavioral phenotypes observed after amphetamine sensitization and conditioned place preference. This will be accomplished by validating, in Specific Aim 1, our viral strategy to deliver CB1 receptors specifically to MSNs in the direct or indirect pathway. In Specific Aim 2, the contribution of diret or indirect MSNs to amphetamine sensitization and conditioned place preference will be determined. In addition, the molecular correlates of amphetamine sensitization will also be examined. Together, the Aims of this study will directly assess how CB1 receptors on MSNs contribute to the behavioral responses to amphetamine.