PET Imaging of Cortical Dopamine Transmission in Cocaine Addiction

可卡因成瘾过程中皮质多巴胺传输的 PET 成像

基本信息

批准号：
7790857
负责人：
RAJESH NARENDRAN
金额：
$ 38.76万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7790857
关键词：
Acute Address Affinity Amphetamines Amygdaloid structure Anterior Area Attention deficit hyperactivity disorder Binding Brain region Cerebellum Cocaine Dependence Communities Corpus striatum structure Data Disease Dopamine Dopamine D2 Receptor Dose Evaluation Functional Magnetic Resonance Imaging Health Hippocampus (Brain)Hour Human Image Imaging Techniques Impairment Investigation Ligands Macaca mulatta Measurement Measures Medial Metabolic Microdialysis Noise Oral Administration Parietal Lobe Pontine structure Positron-Emission Tomography Prefrontal Cortex Raclopride Regulation Relative (related person)Reporting Reproducibility Research Risperidone Role Scanning Schizophrenia Sensory Receptors Signal Transduction Temporal Lobe Testing Thalamic structure Validation addiction base cingulate cortex executive function extracellular human subject imaging modality interest neuropsychiatry nonhuman primate public health relevance radioligand radiotracer receptor receptor density research study single photon emission computed tomography tool transmission process white matter

项目摘要

DESCRIPTION (provided by applicant): Over the last few years, several groups demonstrated that PET and SPECT neuroreceptor imaging techniques can be used, not only to measure receptor parameters, but also to detect acute fluctuations in the concentration of endogenous transmitters in the vicinity of the receptors (for review, see Laruelle, 2000). Using this approach, we and others have reported an abnormal regulation of DA transmission following amphetamine in several neuropsychiatric disorders such as schizophrenia (Breier et al., 1997; Laruelle et al., 1996), attention-deficit hyperactivity disorder (Volkow et al., 2007) and addiction (Malison et al., 1999; Martinez et al., 2007; Volkow et al., 1997). An important limitation of these studies is the fact that measurements of D2 receptors and amphetamine-induced DA release were restricted mostly to the striatum because the ligands used did not provide enough signal to noise ratio to quantify D2 receptors in extrastriatal regions. Given that fMRI/metabolic imaging data suggests a correlation between impairments in executive function and pathological activation of the prefrontal cortex in several neuropsychiatric disroders such as schizophrenia, ADHD and addiction, it is of extreme interest to understand the regulatory role of DA in this particular region (Bush et al., 2008; Callicott et al., 1999; Volkow and Fowler, 2000). We recently demonstrated that the high affinity D2 receptor PET radiotracer [11C]FLB 457 can be used to measure amphetamine-induced DA release in the cortical regions of interest that include the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, medial temporal lobe (which includes the amygdala and hippocampus) and parietal cortex. In this application, we propose to further validate the use of [11C]FLB 457 to detect changes in endogenous DA in the cortical regions in non human primates (specific aim 1) and healthy controls (specific aim 2-4). The proposed validation of [11C]FLB 457 to study amphetamine-induced DA release as outlined in this application will provide the research community with a new tool to study cortical dopamine transmission in both health and disease. PUBLIC HEALTH RELEVANCE: In this application we propose to further validate the use of [11C]FLB 457 to measure amphetamine- induced dopamine (DA) transmission in the human cortex.

描述（由申请人提供）：在过去的几年中，几个小组证明，PET 和 SPECT 神经受体成像技术不仅可以用来测量受体参数，还可以检测神经受体附近内源性递质浓度的剧烈波动。受体（综述，参见 Laruelle，2000）。使用这种方法，我们和其他人报告了在精神分裂症（Breier 等人，1997；Laruelle 等人，1996）、注意力缺陷多动障碍（Volkow 等人，1996）等多种神经精神疾病中使用安非他明后 DA 传输的异常调节。，2007）和成瘾（Malison 等，1999；Martinez 等，2007；沃尔科等人，1997）。这些研究的一个重要限制是 D2 受体和安非他明诱导的 DA 释放的测量主要限于纹状体，因为所使用的配体不能提供足够的信噪比来量化纹状体外区域的 D2 受体。鉴于功能磁共振成像/代谢成像数据表明，在精神分裂症、注意力缺陷多动症和成瘾等几种神经精神疾病中，执行功能损伤与前额皮质病理激活之间存在相关性，因此了解 DA 在这一特定区域的调节作用非常有意义。（Bush 等人，2008 年；Callicott 等人，1999 年；Volkow 和 Fowler，2000 年）。我们最近证明，高亲和力 D2 受体 PET 放射性示踪剂 [11C]FLB 457 可用于测量感兴趣的皮质区域中苯丙胺诱导的 DA 释放，这些区域包括背外侧前额叶皮质、内侧前额叶皮质、前扣带皮层、内侧颞叶（包括杏仁核和海马体）和顶叶皮层。在此应用中，我们建议进一步验证使用 [11C]FLB 457 检测非人类灵长类动物（具体目标 1）和健康对照（具体目标 2-4）皮质区域内源 DA 的变化。如本申请所述，拟对 [11C]FLB 457 进行验证以研究安非他明诱导的 DA 释放，将为研究界提供研究健康和疾病中皮质多巴胺传递的新工具。公共卫生相关性：在此应用中，我们建议进一步验证使用 [11C]FLB 457 来测量人类皮质中安非他明诱导的多巴胺 (DA) 传输。