Effect of Genotype on Resting State Connectivity During Methamphetamine Administration

甲基苯丙胺给药期间基因型对静息态连接的影响

基本信息

批准号：
9981723
负责人：
William Franklin Hoffman
金额：
$ 18.9万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981723
关键词：
Acute Address Adenine Agonist Alleles Amines Amino Acids Amphetamines Attention Behavior Behavioral Berry Blinded Brain Mapping Cell Culture Techniques Chromosome 6 Chronic Codon Nucleotides Cognitive Communities Consent Corpus striatum structure Country Data Dependence Disease Dopamine Economic Burden Enrollment Exhibits Feasibility Studies Functional Magnetic Resonance Imaging Gene Frequency Genes Genetic Genotype Guanine Homozygote Human Individual Intake Intervention Lead Legal Measures Mediating Medical Methamphetamine Methamphetamine dependence Modeling Morbidity - disease rate Mus Neurobiology Oral Patients Pharmaceutical Preparations Pharmacology Placebos Publishing Randomized Receptor Gene Reporting Rest Rewards Ritalin Rodent Seeds Self Administration Signal Transduction Single Nucleotide Polymorphism Techniques Testing Valine Variant Ventral Tegmental Area Visit addiction base behavior measurement behavioral response cognitive control craving density dopamine transporter drug craving economic cost experience genetic variant methamphetamine effect methamphetamine use methamphetamine user neuroadaptation neuroimaging neuropsychiatry novel overexpression pre-clinical receptor receptor expression relating to nervous system response segregation socioeconomics vesicular monoamine transporter

项目摘要

Project Summary Methamphetamine dependence is a widespread problem that crosses socioeconomic boundaries and causes substantial medical morbidity and economic burden. This project uses genetics and neuroimaging techniques to investigate the neurobiology of addiction to methamphetamine as it relates to the TAAR1 trace amine receptor. We hypothesize that individuals with a common TAAR1 genetic variant (v288v) will have a blunted response to methamphetamine on tests of attention and cognitive control as well as on striato-limbic resting state functional connectivity (RSFC). SA 1. Determine the influence of htaar1 common variant (CV) vs. wild type (WT) genotype on RSFC and craving in chronic MUD. SA 2: Determine the effect of acute oral MA or placebo (PBO) administration on the interaction of htaar1 CV vs. WT genotype on RSFC, craving, cognitive control, attention and subjective experience in MUD. This project will consent and enroll up to 100 subjects who will be screened for TAAR1 genotype and placed into one of two groups: one which will include subjects who are wild type (WT) for the TAAR1 gene and those who are either homozygous or heterozygous for the CV, v288v. Others will be screened out of the study. A partner lab will determine genotype so that study staff and subjects will be blinded to genotype. Subjects will be administered methamphetamine and placebo in a blinded, randomized manner over two visits and evaluated with resting state fMRI, subjective effects and behavioral tasks. RSFC comparisons of meth versus placebo and comparisons of WT versus CV groups will be evaluated.

项目摘要甲基苯丙胺依赖性是一个跨越社会经济边界和原因的广泛问题大量医疗发病率和经济负担。该项目使用遗传学和神经影像学技术研究与TAAR1痕量胺相关的甲基苯丙胺成瘾的神经生物学受体。我们假设具有常见TAAR1遗传变异（V288V）的个体将有一个钝的对甲基苯丙胺的反应以及认知控制测试以及纹状体静止状态功能连接（RSFC）。 SA 1。确定HTAAR1公共变体（CV）与野生型（WT）基因型对RSFC的影响渴望在慢性泥浆中。 SA 2：确定急性口服MA或安慰剂（PBO）给药对HTAAR1 CV相互作用的影响与RSFC，渴望，认知控制，注意力和主观经验的WT基因型与WT基因型。该项目将同意并注册100名受试者，他们将被筛选为TAAR1基因型并放置分为两组之一：其中包括野生型（WT）的受试者对于CV，V288V，他们是纯合或杂合。其他人将被筛选出研究。一个合作伙伴实验室将确定基因型，以便研究人员和受试者对基因型视而不见。受试者会在两次访问中以盲，随机的方式施用甲基苯丙胺和安慰剂，然后通过静止状态fMRI，主观效果和行为任务进行评估。 RSFC的甲基甲基对比比较将评估WT与CV组的安慰剂和比较。