Synaptic Vesicle Density in Cannabis Dependence

大麻依赖性中的突触小泡密度

基本信息

批准号：
9387557
负责人：
DEEPAK Cyril D'SOUZA
金额：
$ 25.13万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9387557
关键词：
Abstinence Acute Adolescence Adolescent Adult Affect Age Age-Years Alzheimer&apos s Disease Animals Anterior Anticonvulsants Applications Grants Auditory Binding Brain Brain imaging Brain region CNR1 gene Cannabinoids Cannabis Chronic Cognition Cognitive deficits Data Development Distal Electroencephalography Electrophysiology (science)Event Exposure to Funding Globus Pallidus Glycoproteins Hippocampus (Brain)Histologic Human Image In Vitro Individual Insula of Reil Keppra Kinetics Legal Levetiracetam Ligand Binding Link Magnetic Resonance Imaging Marijuana Dependence Measures Medial Medical Membrane Proteins Memory Memory impairment Metabolism Methods Modeling Morphology Outcome Parahippocampal Gyrus Penetration Perception Peripheral Pharmaceutical Preparations Phase Population Positron-Emission Tomography Protein Isoforms Proteins Proxy Research Resolution Risk Rodent Safety Scalp structure Schizophrenia Signal Transduction Specificity Spices Structure Surface Synapses Synaptic Vesicles Synaptophysin Teenagers Temporal Lobe Testing Tracer Verbal Learning Vertebral column analog cingulate cortex cognitive function density early adolescence emerging adult gray matter illicit drug use in vivo marijuana legalization marijuana use neuropsychiatric disorder novel parametric imaging postsynaptic putamen radioligand relating to nervous system response risk perception synthetic cannabinoid virtual young adult

项目摘要

PROJECT SUMMARY AND ABSTRACT Background: Cannabis is the most commonly used illicit drug by young people. The potency of cannabis has increased and so has the use of highly potent synthetic cannabinoids (`Spice'). Furthermore, the “medical” and recreational use of cannabis is increasingly being legalized across the U.S. Perceptions of the risks of cannabis use amongst teenagers has declined over the past decade . The initiation of cannabis use typically occurs during adolescence and young adulthood, when the brain is still developing and is most vulnerable to insults, particularly drugs. Therefore, it is important to understand the consequences of chronic cannabinoid exposure on the structure and function of the brain. Repeated administration of cannabinoids to both rodents has been shown to lower synaptic density, but this has yet to be studies in humans. We recently developed [11C]-UCB-J, a tracer for imaging of the synaptic vesicle protein SV2A in vivo. The purpose of this exploratory study is to compare synaptic density in cannabis dependent subjects (CDs) and healthy controls (HCs) and to relate changes in synaptic density to proximal and distal measures of brain activity, namely evoked ɣ oscillations in the EEG and verbal memory. Furthermore, the relationship between [11C]-UCB-J binding, evoked ɣ oscillations, verbal memory, and measures of cannabis exposure (age of first use and lifetime exposure) will be explored. Hypotheses: Compared to HCs, CDs will show 1) ↓ [11C]-UCB-J binding, 2) ↑ deficits in measures of evoked ɣ oscillations, and 3) ↑ deficits in verbal memory. In CD subjects, lower [11C]UCB-J binding will be positively correlated with earlier age of initiation of cannabis use, lifetime cannabis exposure, worse verbal memory and greater deficits in ɣ oscillations. Methods: We will compare synaptic density in CDs (n=12) vs. HCs (n=12) using [11C]- UCB-J and the High Resolution Research Tomograph. CDs and HCs will also be compared on measures of evoked ɣ oscillations (auditory steady state response: ASSR) and verbal memory (Rey Auditory Verbal Learning Task: RAVLT). The relationship between [11C]- UCB-J binding, evoked ɣ oscillations, verbal memory, and measures of cannabis exposure (age of initiation of use and lifetime exposure) will be explored. Pilot data: To demonstrate feasibility, CDs (n=2) and HC (n=6) have been studied; CDs showed reduced SV2A binding of 10% or more (i.e., greater than the margin of test-retest variability) in several brain regions.

项目概要和摘要背景：大麻是年轻人最常用的非法药物。增加，高效合成大麻素（“香料”）的使用也随之增加。在美国，娱乐性使用大麻越来越合法化。对风险的看法青少年使用大麻过去十年有所下降通常开始使用大麻发生在青春期和成年早期，此时大脑仍在发育，最容易受到因此，了解慢性大麻素的后果非常重要。对两种啮齿类动物重复施用大麻素对大脑结构和功能的影响。已被证明可以降低突触密度，但这尚未在人类中进行研究。 [11C]-UCB-J，一种用于体内突触小泡蛋白 SV2A 成像的示踪剂本探索性的目的。研究旨在比较大麻依赖受试者（CD）和健康对照（HC）的突触密度，并突触密度的变化与大脑活动的近端和远端测量有关，即诱发 ɣ 脑电图和言语记忆中的振荡此外，[11C]-UCB-J 结合之间的关系，诱发的 ɣ 振荡、言语记忆和大麻暴露测量（首次使用年龄和一生暴露）将被探索。假设：与 HC 相比，CD 将显示 1) ↓ [11C]-UCB-J 结合，2) ↑ 诱发 ɣ 测量值的缺陷振荡，以及 3) ↑ 在 CD 受试者中，较低的 [11C]UCB-J 结合将呈阳性。与开始使用大麻的年龄较早、终生接触大麻、言语记忆力较差以及 ɣ 振荡的更大赤字。方法：我们将使用以下方法比较 CD (n=12) 与 HC (n=12) 中的突触密度 [11C]- UCB-J 和高分辨率研究断层扫描仪也将在诱发 ɣ 振荡的测量方面进行比较。（听觉稳态反应：ASSR）和言语记忆（Rey 听觉言语学习任务：RAVLT）。之间的关系 [11C]- UCB-J 结合、诱发 ɣ 振荡、言语记忆和大麻测量将探讨暴露（开始使用的年龄和终生暴露）。试点数据：为了证明可行性，对 CD (n=2) 和 HC (n=6) 进行了研究，结果显示 CD 减少了；在几个大脑区域中 SV2A 结合率为 10% 或更高（即大于重测变异性的范围）。