Interactions of Ethanol & Cocaine Self-Administration in Monkeys

乙醇的相互作用

• 批准号: 9502948
• 负责人: Paul W. Czoty
• 金额: $ 34.2万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/9502948
• 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; Exposure to; Failure; Food; Home environment; Human; Image; Imaging Techniques; 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; Schedule; Selection for Treatments; Self Administration; Self-Administered; Testing; Time; Training; Translating; Treatment Effectiveness; Work; alcohol effect; alcohol exposure; alcohol reinforcement; alcohol response; alcohol seeking behavior; behavioral study; chronic alcohol ingestion; clinical efficacy; cocaethylene; cocaine use; design; dopamine D3 receptor; dopamine system; drinking; experience; imaging study; individual patient; nonhuman primate; novel; personalized medicine; pre-clinical; pre-clinical research; preclinical study; receptor; research clinical testing; response; tool

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.

项目摘要 可卡因滥用仍然是一个重大的公共卫生问题，没有广泛有用的问题 药物治疗。已经产生了许多尚未转化为成功的临床前线。 可卡因依赖的药物。造成这种失败的原因之一可能是，尽管多达90％的可卡因 施虐者还滥用酒精，药物开发过程（临床前动物实验和 假定药物的早期临床测试是在没有酒精暴露的受试者中进行的。什么 关于可卡因/乙醇相互作用的数据很少，这表明这可能代表了重要的 混淆；乙醇可以增强可卡因在动物和人类中的某些作用，并减轻其他可卡因。 此外，最近的临床试验表明，酒精依赖史可以降低 减少可卡因使用的药物。拟议的研究旨在确定长期乙醇 饮酒改变了非人类灵长类动物模型中可卡因的滥用相关作用，反之亦然。首先，我们会的 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）的平行脑成像研究将表征如何 乙醇，可卡因或组合的自我给药改变了脑D2型和D3的可用性 多巴胺受体与可卡因和乙醇滥用有关，并已被建议 作为药物疗法开发的靶标。然后，我们将检查这些大脑成像是否测量 与潜在药物疗法降低可卡因使用的能力相关。重要的关系 会表明，医生可以将这种措施用作行为表型的生物标志物和 用于治疗有效性。最后，自我管理可卡因对随后的乙醇自我的影响 将确定管理。综上所述，这些研究将提供描述的新型可翻译数据 乙醇和可卡因对彼此与滥用相关的影响的影响，并确切地表征如何 这些药物的联合使用会改变DA受体，将提供新的信息以帮助指导治疗 同时滥用酒精的大多数可卡因使用者的决定。