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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：
8869751
负责人：
MATTHEW D BUDDE
金额：
$ 22.95万
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 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8869751
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 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 public health relevance 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（由申请人提供）：药物使用障碍（SUD）是创伤性脑损伤（TBI）后常见的合并症，即使患者既往没有药物使用史。然而，TBI 的神经系统影响在多大程度上促进 SUD 的发展尚不清楚。长期目标是了解脑损伤如何改变神经和精神功能。本研究的目的是阐明轻度 TBI (mTBI)、成瘾表型和中皮质边缘功能之间的关系。核心假设是 mTBI 会导致药物成瘾风险升高和中皮质边缘回路发生变化。这一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。拟议研究的基本原理是，了解 mTBI 的神经学后果将有助于制定 mTBI 患者的治疗策略。为了分离神经系统影响，我们提出了一种啮齿动物模型，以便能够研究 mTBI 对具有相似环境史的未用药生物体的影响。我们的假设得到了流行病学和初步数据的支持，并将在两个具体目标上进行测试：1）确定 mTBI 对药物自我给药、寻求和复发的影响； 2) 确定 mTBI 和可卡因对与毒品寻找有关的大脑网络的影响。在目标 1 中，将在爆炸力诱发轻度 TBI 后测量大鼠的可卡因自我施用和药物寻找行为。在目标 2 中，将在 mTBI 和可卡因自我给药之前和之后进行结构和功能成像研究。该方法具有创新性，因为它将把来自受控且可重复的临床前模型的转化成像和行为数据贡献给一直由人类成像和相关研究主导的研究领域。该项目意义重大，因为它将启动一系列研究，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药物寻求行为。这项工作预计将有助于基础研究的发展，有助于开发治疗 TBI 后共病心理和精神疾病的方法。