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

• 批准号: 9488672
• 负责人: MATTHEW D BUDDE
• 金额: $ 0.79万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 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/9488672
• 关键词: 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; National Institute of Drug Abuse; Nervous System Physiology; Neurologic; Neurologic Effect; Neuropsychology; Organism; Outcome; Patients; Pharmaceutical Preparations; Phenotype; Pre-Clinical Model; Predisposition; Prefrontal Cortex; Public Health; Rattus; Recording of previous events; Relapse; Reproducibility; 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; human imaging; imaging study; innovation; mild traumatic brain injury; neurobehavioral; neuroimaging; patient population; pre-clinical; preclinical study; programs; prospective; public health relevance; standard care; therapeutic development; therapy development

 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.



项目成果

Repeated blast mild traumatic brain injury and oxycodone self-administration produce interactive effects on neuroimaging outcomes.

• DOI: 10.1111/adb.13134
• 发表时间: 2022-03
• 期刊: Addiction biology
• 影响因子: 3.4
• 作者: Muelbl MJ;Glaeser BL;Shah AS;Chiariello RA;Nawarawong NN;Stemper BD;Budde MD;Olsen CM
• 通讯作者: Olsen CM

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics.

基于头部旋转加速度特征的啮齿动物模型中脑震荡后行为变化的预测。

• DOI: 10.1007/s10439-016-1647-x
• 发表时间: 2016
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Stemper,BrianD;Shah,AlokS;Chiariello,Rachel;Olsen,ChristopherM;Budde,MatthewD;Glavaski-Joksimovic,Aleksandra;McCrea,Michael;Kurpad,ShekarN;Pintar,FrankA
• 通讯作者: Pintar,FrankA

Chronicity of repeated blast traumatic brain injury associated increase in oxycodone seeking in rats.

慢性反复爆炸性脑损伤与大鼠寻求羟考酮的增加有关。

• DOI: 10.1016/j.bbr.2022.114181
• 发表时间: 2023
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Chiariello,Rachel;McCarthy,Cassandra;Glaeser,BreannaL;Shah,AlokS;Budde,MatthewD;Stemper,BrianD;Olsen,ChristopherM
• 通讯作者: Olsen,ChristopherM