CB1 receptor in medium spiny neurons in amphetamine sensitization

安非他明致敏中中棘神经元中的 CB1 受体

• 批准号: 8591813
• 负责人: Brian Robert Haas
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591813
• 关键词: Affect; Aftercare; Agonist; Amphetamines; Antibodies; Area; Backcrossings; Behavior; Behavioral; Brain; Brain region; CNR1 gene; Cannabinoids; Cells; Clinical; Corpus striatum structure; Data; Development; Dopamine; Drug Addiction; Dynorphins; Enkephalins; FOS gene; Future; Genetic; Globus Pallidus; Glutamates; Goals; Guanosine Triphosphate; Immunohistochemistry; Injection of therapeutic agent; Interneurons; Knock-in Mouse; Lead; Measures; Mediating; Methods; Modeling; Molecular; Mus; National Research Service Awards; Neurons; Parvalbumins; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Play; Population; Presynaptic Terminals; Publishing; Research; Research Personnel; Role; Series; Somatostatin; Specificity; Substance P; Substantia nigra structure; Synapses; Terminator Codon; Testing; Thalamic structure; Training; Transgenic Mice; United States; Viral; Viral Vector; Virus; addiction; base; brain cell; cell type; cost; dopaminergic neuron; drug seeking behavior; genetic manipulation; molecular marker; novel therapeutics; preference; promoter; protein expression; public health relevance; receptor; research study; response; selective expression; skills; success; therapy outcome; vector control

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.

药物成瘾，包括安非他明及其衍生物，每年花费美国约1810亿美元。不幸的是，药物寻求行为和成瘾的分子基础仍然知之甚少，还有很多需要研究。因此，必须确定和测试新的药物成瘾治疗方法，特别是安非他明。为了做到这一点，有必要更好地了解参与这种现象的大脑区域和细胞类型。最近令人兴奋的研究已经确定，在成瘾相关行为的背景下，一些行为表型由CB1受体控制。这些受体在GABA能中型棘神经元（MSN）上以高水平表达。这个NRSA的目标是更好地了解如何CB1受体MSNs上表达的苯丙胺致敏和条件性位置偏爱后观察到的行为表型作出贡献。这将通过在特定目标1中验证我们的病毒策略来实现，该策略将CB1受体以直接或间接途径特异性地递送至MSN。在具体目标2中，将确定直接或间接MSN对苯丙胺致敏和条件性位置偏爱的贡献。此外，还将研究安非他明致敏的分子相关性。总之，本研究的目的将直接评估MSN上的CB1受体如何促进对苯丙胺的行为反应。