PET AND SPECT IMAGING IN ALCOHOLIC SMOKERS

酗酒者的 PET 和 SPECT 成像

基本信息

批准号：
6168167
负责人：
JULIE K STALEY
金额：
$ 12.82万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-01 至 2004-07-31
项目状态：
已结题

项目摘要

This MRSDA K0l application requests support to promote the candidate's development into an independent investigator in the application of positron emission tomography (PET) and single photon emission tomography (SPECT) neuroimaging methods to the neurochemistry of alcohol and nicotine dependence. The candidate's proposed Career Development and Research Plans will be facilitated by ongoing mentoring relationships with Drs. Stephanie O'Malley and Robert B Innis, established senior scientists with internationally recognized accomplishments in clinical neuropsychopharmacology of alcohol dependence and PET and SPECT imaging, respectively. A comprehensive five-year Career Development Plan will provide the candidate with the multi- disciplinary skills required to ultimately lead an independent and highly productive research program in brain imaging of substance dependence. This plan has been carefully devised to satisfy specific career development needs in the following major areas: l) clinical research methods in alcoholism; 2) use of radioisotopes in humans; 3) imaging instrumentation and analysis; 4) radiotracer development, pharmacokinetic and tracer kinetic modeling; and 5) quantitative skills and biostatistics. Formal training in these highly specialized areas will be achieved through an intensive curriculum of seminars, tutorials, extramural didactics, and research studies. Three specific aims are proposed which seek to assess the status of key dopaminergic and serotonergic synaptic markers in actively dependent alcoholic smokers and nonsmokers and nonalcoholic smokers and nonsmokers. We propose l) to determine if striatal DA transporters are decreased in alcoholics and to delineate the effects of nicotine in the alcoholic and nonalcoholic populations as assessed via SPECT using [123I]beta-CIT; 2) To determine if brainstem 5-HT transporters are elevated in actively dependent alcoholics and to distinguish the effects of nicotine in alcoholic and nonalcoholic populations, as assessed via SPECT using [123I]beta-CIT and 3) To determine if cortical 5HT2A receptors are differentially regulated in actively dependent alcoholic smokers and alcoholic nonsmokers as assessed via PET using [18F]deuteroaltanserin. The findings from these studies will offer insight into the neurochemical alterations associated with dual alcohol and nicotine dependence which may guide the development of more effective pharmacotherapies for these devastating brain disorders.

这项MRSDA K0L应用要求支持将候选人的发展促进独立研究者，以应用正电子发射断层扫描（PET）和单个光子发射断层扫描（SPECT）神经影像学方法，以促进酒精和尼古丁依赖性的神经化学方法。候选人提议的职业发展和研究计划将通过与DRS的持续指导关系来促进。斯蒂芬妮·奥马利（Stephanie O'Malley）和罗伯特·B·内尼斯（Robert B Innis）成立了高级科学家，分别在国际上认可的酒精依赖性临床神经心理药理学成就，宠物和SPECT成像。一项综合的五年职业发展计划将为候选人提供最终领导独立且高效的研究计划的多学科技能，以实质性依赖的大脑成像。该计划经过精心设计，以满足以下主要领域的特定职业发展需求：l）酒精中毒中的临床研究方法； 2）在人类中使用放射性同位素； 3）成像仪器和分析； 4）放射性示踪剂的发育，药代动力学和示踪剂动力学建模； 5）定量技能和生物统计学。这些高度专业的领域的正式培训将通过大量的研讨会，教程，壁外教学学和研究研究来实现。提出了三个特定的目标，试图评估积极依赖的酒精吸烟者，非吸烟者以及非酒精吸烟者和非吸烟者的关键多巴胺能和血清素能突触标记的状态。我们建议l）确定酗酒者中纹状体DA转运蛋白的转运蛋白转运蛋白是否会减少，并描绘出使用[123i] beta-cit通过SPECT评估的酒精和非酒精种群中尼古丁的影响； 2) To determine if brainstem 5-HT transporters are elevated in actively dependent alcoholics and to distinguish the effects of nicotine in alcoholic and nonalcoholic populations, as assessed via SPECT using [123I]beta-CIT and 3) To determine if cortical 5HT2A receptors are differentially regulated in actively dependent alcoholic smokers and alcoholic nonsmokers as assessed via PET using [18F]deuteroaltanserin.这些研究的发现将为与双重酒精和尼古丁依赖性相关的神经化学改变提供深入的见解，这可以指导为这些毁灭性脑疾病的更有效的药物疗法开发。