Interactions of Ethanol & Cocaine Self-Administration in Monkeys

乙醇的相互作用

基本信息

批准号：
9175685
负责人：
Paul W. Czoty
金额：
$ 45.45万
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：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9175685
关键词：
Address Affect Alcohol abuse Alcohol consumption Alcohol dependence Alcohols Animal Experiments Animal Model Animals Attenuated Behavioral Biological Markers Blood Brain Brain imaging Buprenorphine Chronic Clinic Clinical Clinical Trials Cocaine Cocaine Abuse Cocaine Dependence Cocaine Users Control Groups DRD2 gene Data Development Dextroamphetamine Diagnosis Disease Dopamine Dopamine Receptor Dose Drug usage Ethanol Failure Food Home environment Human Image Imaging Techniques Intake Laboratory Finding Long-Term Effects Macaca mulatta Maintenance Measures Mediating Modafinil Modeling Monkeys Pharmaceutical Preparations Pharmacotherapy Phenotype Physicians Positron-Emission Tomography Procedures Process Production Psychological reinforcement Public Health Raclopride Recording of previous events Research Research Design Schedule Selection for Treatments Self Administration Self-Administered Testing Time Training Translating Treatment Effectiveness Work alcohol effect alcohol exposure behavioral study chronic alcohol ingestion clinical efficacy cocaethylene cocaine use design dopamine D3 receptor dopamine system drinking experience individual patient nonhuman primate novel personalized medicine pre-clinical pre-clinical research preclinical study receptor research clinical testing response tool

项目摘要

Project Summary Cocaine abuse remains a significant public health problem for which there are no widely useful pharmacotherapies. Many preclinical leads have been generated that have not translated into successful medications for cocaine dependence. One reason for this failure may be that, although up to 90% of cocaine abusers also abuse alcohol, the medications development process (both preclinical animal experiments and early clinical testing of putative medications) has taken place in subjects with no exposure to alcohol. What little data that exists regarding cocaine/ethanol interactions suggests that this may represent a significant confound; ethanol can enhance some effects of cocaine in animals and humans and attenuate others. Moreover, recent clinical trials have shown that a history of alcohol dependence can reduce the ability of medications to decrease cocaine use. The proposed studies are designed to determine how long-term ethanol drinking alters the abuse-related effects of cocaine and vice versa in nonhuman primate models. First, we will determine whether prior ethanol exposure alters acquisition and maintenance (6 months) of cocaine self- administration. Parallel brain imaging studies using positron emission tomography (PET) will characterize how self-administration of ethanol, cocaine or the combination changes the availability of brain D2-like and D3 dopamine receptors, which have been implicated in both cocaine and ethanol abuse and have been suggested as targets for pharmacotherapy development. We will then examine whether these brain imaging measures correlate with the ability of potential pharmacotherapies to decrease cocaine use. Significant relationships would indicate that such measures could be used by physicians as biomarkers for behavioral phenotypes and for treatment effectiveness. Finally, the effects of self-administered cocaine on subsequent ethanol self- administration will be determined. Taken together, these studies will provide novel translatable data describing the effects of ethanol and cocaine on each other's abuse-related effects and, by characterizing precisely how combined use of these drugs alters DA receptors, will provide novel information to help guide treatment decisions for the large majority of cocaine users who concurrently abuse alcohol.

项目概要可卡因滥用仍然是一个重大的公共卫生问题，目前还没有广泛有效的治疗方法药物疗法。许多临床前线索尚未转化为成功可卡因依赖药物。失败的原因之一可能是，尽管高达 90% 的可卡因滥用者还滥用酒精、药物开发过程（临床前动物实验和推定药物的早期临床测试）已在未接触酒精的受试者中进行。什么关于可卡因/乙醇相互作用的数据很少，表明这可能代表了一个重要的混淆；乙醇可以增强可卡因对动物和人类的某些作用并减弱其他作用。此外，最近的临床试验表明，酒精依赖史会降低酒精依赖的能力。减少可卡因使用的药物。拟议的研究旨在确定乙醇的长期效果如何在非人类灵长类动物模型中，饮酒会改变可卡因滥用相关的影响，反之亦然。首先，我们将确定先前的乙醇暴露是否会改变可卡因自我的获取和维持（6个月）行政。使用正电子发射断层扫描 (PET) 的并行脑成像研究将描述如何自行服用乙醇、可卡因或其组合会改变大脑 D2 样和 D3 的可用性多巴胺受体，与可卡因和乙醇滥用有关，并已被认为作为药物治疗开发的目标。然后我们将检查这些脑成像是否测量与潜在药物疗法减少可卡因使用的能力相关。重要关系将表明医生可以使用此类措施作为行为表型的生物标志物以达到治疗效果。最后，自我施用可卡因对随后的乙醇自我施用的影响将确定行政管理。总而言之，这些研究将提供新颖的可翻译数据来描述乙醇和可卡因对彼此滥用相关影响的影响，并通过准确描述如何这些药物的联合使用会改变 DA 受体，将提供新的信息来帮助指导治疗绝大多数同时酗酒的可卡因使用者的决定。