Neurobiological Correlates of Cocaine Abuse

可卡因滥用的神经生物学相关性

基本信息

批准号：
7600548
负责人：
LINDA J. PORRINO
金额：
$ 41.46万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-07-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7600548
关键词：
Abstinence Agonist Amphetamines Animal Model Animals Behavioral Brain Cerebrum Chronic Cocaine Cocaine Abuse Cues Data Deoxyglucose Dependence Dextroamphetamine Dopamine Drug Exposure Drug usage Drug user Evaluation Funding Glucose Goals Human Image Intervention Investigation Legal Life Experience Measures Metabolism Methods Modeling Modification Monkeys Neurobiology Norepinephrine Oral Pattern Pharmaceutical Preparations Population Prevention Public Health Recording of previous events Regulation Replacement Therapy Reporting Research Personnel Residual state Role Self Administration Stimulus Structure System Therapeutic Treatment Protocols United States behavior influence cocaine exposure cocaine use effective therapy experience imaging modality neuroadaptation non-drug nonhuman primate noradrenergic norepinephrine system programs response treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Studies of cocaine abusers often show evidence of decreased brain function as well as abnormalities in brain structure. Attributing these deficits directly to the chronic abuse of cocaine itself can be quite challenging in this population. Cocaine abusers often use multiple legal and illegal drugs over varying durations, have co-morbid psychiatric conditions, and experience different life experiences than their non-drug using controls. In addition, many of these differences may have pre-dated any drug use. One approach to this challenge is the use of animal models in which factors can be varied systematically and the role of each factor determined with greater confidence. During the past funding period we have employed a non-human primate model of cocaine self-administration to characterize the changes in the network of changes in cerebral metabolism that accompanies chronic cocaine exposure and the modifications of these changes with abstinence. In the present application we propose to continue use of this model to answer the following questions. First, do the neuroadaptations in brain structure and function in response to cocaine result in residual changes in basal brain activity? Second, how do these neuroadaptations influence the functional response to drug-associated cues and how does this response compare to the response to cocaine itself? Third, what is the neurobiological impact of a pharmacological intervention with replacement therapy in animals chronically exposed to cocaine? These studies will combine careful behavioral analysis with detailed imaging investigations to answer these questions. Despite significant treatment and prevention efforts, cocaine abuse remains an ongoing public health problem. Completion of the studies proposed in this application will provide the data essential for more effective evaluations of treatment strategies for cocaine abuse and dependence. In addition, these studies will provide new information about the interaction of potential pharmacological therapies with the brain changes associated with chronic cocaine exposure, as well as the persistence of these changes over the course of abstinence from drug use.

描述（由申请人提供）：可卡因施虐者的研究通常显示出脑功能下降以及大脑结构异常的证据。将这些赤字直接归因于对可卡因本身的长期虐待，在这个人群中可能具有挑战性。可卡因施虐者经常在不同的持续时间内使用多种法律和非法药物，具有合并的精神病状况，并且与使用控件的非药物相比，他们的生活经历不同。此外，这些差异中的许多可能已经预先预先使用任何药物。应对这一挑战的一种方法是使用动物模型，在这种模型中可以系统地变化，并且每个因素的作用都以更大的置信度确定。在过去的资金期间，我们采用了一种非人类的可卡因自我管理的灵长类动物模型来表征伴随慢性可卡因暴露的大脑代谢变化网络的变化，以及这些变化的修饰。在本应用程序中，我们建议继续使用此模型来回答以下问题。首先，响应可卡因的大脑结构和功能的神经照射是否会导致基础脑活动的残留变化？其次，这些神经适用于对与药物相关线索的功能反应如何与对可卡因本身的反应相比如何？第三，在长期暴露于可卡因的动物中，药理学干预对替代疗法的神经生物学影响是什么？这些研究将仔细的行为分析与详细的成像调查相结合，以回答这些问题。尽管有重大的治疗和预防工作，但可卡因滥用仍然是一个持续的公共卫生问题。在本申请中提出的研究的完成将为可卡因滥用和依赖性的治疗策略提供更有效评估的必要数据。此外，这些研究将提供有关潜在药理疗法与慢性可卡因暴露相关的大脑变化的相互作用的新信息，以及这些变化在禁止药物使用的过程中的持续性。