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：
7934671
负责人：
RAJESH NARENDRAN
金额：
$ 51.45万
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/7934671
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，几个小组表明，PET和SPECT神经受体成像技术不仅可以测量受体参数，还可以检测到受体附近内源性发射器浓度的急性波动（有关综述，请参见Laruelle，2000年）。使用这种方法，我们和其他人报道了在几种神经精神疾病（如精神分裂症）中对DA传播的异常调节（Breer等，1997; Laruelle等，1996），注意缺陷多动障碍障碍（Volkow等人，2007年，2007年）和成瘾（Malison and al。 1997）。这些研究的一个重要局限性是，D2受体和苯丙胺诱导的DA释放的测量主要限制在纹状体上，因为所使用的配体没有提供足够的信号与噪声比来量化外生区域的D2受体。鉴于fMRI/代谢成像数据表明，执行功能的损害与额叶前皮层的病理激活之间存在相关性，例如精神分裂症，ADHD和成瘾等几种神经精神上的疾病，因此，它具有极大的兴趣，可以极大地了解DA在这一特定地区的调节作用（Bush等人（Bush et al an al al an al al and al and al and al and al and al and and al and al and al and al and al and al and and and and and and and and and and and and and and and and and and and and and and and and and and al and and alkic and all;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引起的DA释放，其中包括背侧前额叶皮层，内侧前额叶皮质，前额叶皮层，前毛状皮质，甲状腺膜状皮质，包括ammeal superal and amyg and amygala and amygala and amygala and Amyglaa，皮质。在此应用中，我们建议进一步验证[11C] FLB 457来检测非人类灵长类动物皮质区域内源性DA的变化（特定的目标1）和健康的对照（特定目标2-4）。 [11C] FLB 457的拟议验证以研究苯丙胺诱导的DA释放，如本应用程序所述，将为研究界提供一种新的工具，用于研究健康和疾病中的皮质多巴胺传播。公共卫生相关性：在此应用中，我们建议进一步验证[11C] FLB 457来测量人类皮质中的苯丙胺诱导的多巴胺（DA）传播。