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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.