Mild TBI: Effects on addiction-related phenotypes and mesocorticolimbic function

轻度 TBI：对成瘾相关表型和中皮质边缘功能的影响

基本信息

批准号：
9025768
负责人：
MATTHEW D BUDDE
金额：
$ 19.03万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9025768
关键词：
Accounting Addictive Behavior Affect Alcohol consumption Animals Anterograde Amnesia Basic Science Behavioral Biological Markers Blast Cell Blast Injuries Brain Brain Injuries Cocaine Comorbidity Correlative Study Data Development Diffusion Magnetic Resonance Imaging Disease Drug Addiction Drug Exposure Drug abuse Drug usage Emotional Disturbance Epidemiology Functional Imaging Goals Health Human Image Impaired cognition Incidence Injury Intake Intervention Investigation Knowledge Lesion Magnetic Resonance Imaging Measures Medial Mental disorders Microscopic Military Personnel Mission Modeling Nervous System Physiology Neurologic Organism Outcome Patients Pharmaceutical Preparations Phenotype Pre-Clinical Model Predisposition Prefrontal Cortex Public Health Rattus Recording of previous events Relapse Research Research Design Resolution Risk Rodent Rodent Model Role Self Administration Substance Use Disorder Substance abuse problem Symptoms TBI Patients Techniques Testing Time Traumatic Brain Injury Veterans Work addiction brain abnormalities brain circuitry cocaine exposure cocaine use combat drug seeking behavior experience field study frontal lobe human data innovation mild traumatic brain injury neurobehavioral neuroimaging neuropsychological patient population pre-clinical preclinical study programs psychologic standard care therapeutic development therapy development

项目摘要

DESCRIPTION (provided by applicant): Substance use disorder (SUD) is a frequent comorbidity following traumatic brain injury (TBI), even in patients without a previous history of drug use. However, the extent to which the neurological effects of TBI contribute to the development of SUD is unknown. The long-term goal is to understand how brain injury alters neurological and psychiatric function. The objective of the proposed research is to elucidate the relationship between mild TBI (mTBI), addictive phenotypes, and mesocorticolimbic function. The central hypothesis is that mTBI results in elevated risk for drug addiction and changes in mesocorticolimbic circuitry. This hypothesis is supported by correlative data from human studies and by preliminary imaging data using a preclinical mTBI model. The rationale for the proposed research is that understanding the neurological consequences of mTBI will aid in the development of therapeutic strategies for mTBI patients. To isolate neurological effects, we propose a rodent model to enable investigation of the effects of mTBI in drug naïve organisms with similar environmental histories. Our hypothesis is supported by epidemiological and preliminary data and will be tested in two specific aims: 1) Identify the impact of mTBI on drug self-administration, seeking, and relapse; and 2) Determine the effects of mTBI and cocaine on brain networks implicated in drug seeking. In Aim 1, cocaine self-administration and drug seeking will be measured in rats following mild TBI induced by blast forces. In Aim 2, structural and functional imaging studies will be performed before and after mTBI and cocaine self-administration. The approach is innovative because it will contribute translational imaging and behavioral data from a controlled and reproducible preclinical model to a field of study that has been dominated by human imaging and correlative studies. The project is significant because it will initiate a course of research that will reveal mechanisms of TBI sequelae and how these sequelae can influence drug intake and drug seeking behaviors. This work is expected to contribute to a body of basic research that will aid in the development of treatments for co-morbid psychological and psychiatric disorders following TBI.

描述（由适用提供）：即使在没有以前的药物使用史的患者中，脑损伤（TBI）也经常是合并症（TBI）后的合并症。但是，TBI的神经系统作用在多大程度上有助于SUS的发展。长期目标是了解脑损伤如何改变神经系统和精神病功能。拟议的研究的目的是阐明轻度TBI（MTBI），添加剂表型和中皮质糖函数之间的关系。中心假设是MTBI导致药物成瘾的风险升高和中皮质胶质电路的变化。该假设得到了人类研究的相关数据和使用临床前MTBI模型的初步成像数据的支持。拟议的研究的理由是，了解MTBI的神经系统后果将有助于为MTBI患者制定治疗策略。为了隔离神经系统作用，我们提出了一个啮齿动物模型，以使MTBI在具有相似环境历史的幼稚生物体中投资。我们的假设得到了流行病学和初步数据的支持，并将以两个具体目的进行检验：1）确定MTBI对药物自我给药，寻求和继电器的影响； 2）确定MTBI和可卡因对寻求药物实施的脑网络的影响。在AIM 1中，可卡因自我给药和寻求药物将在爆炸力引起的轻度TBI之后在大鼠中测量。在AIM 2中，将在MTBI和可卡因自我管理之前和之后进行结构和功能成像研究。该方法具有创新性，因为它将从受控且可重复的临床前模型到由人类成像和正确研究主导的研究领域，从而贡献转化成像和行为数据。该项目很重要，因为它将启动一系列研究，以揭示TBI后遗症的机制，以及这些后遗症如何影响药物摄入和寻求药物的行为。预计这项工作将有助于一系列基础研究，该研究将有助于开发TBI后的心理和精神疾病的治疗方法。