Behavioral Studies of Opiate Tolerance and Dependence

阿片类药物耐受性和依赖性的行为研究

• 批准号: 6616665
• 负责人: ALICE M YOUNG
• 金额: $ 37.03万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6616665
• 关键词: behavior prediction; behavioral /social science research tag; conditioning; drug /alcohol abstinence; drug abuse chemotherapy; endogenous opioid; laboratory rat; morphine; narcotic antagonists; operant conditionings; opiate alkaloid; opioid receptor; pigeons; psychopharmacology; receptor expression; substance abuse related behavior

DESCRIPTION (provided by applicant): Current treatments for human opioid abuse incorporate a variety of chronic pharmacotherapies, including methadone maintenance and newer therapies incorporating low efficacy opioid agonists (e.g., buprenorphine) or opioid antagonists (e.g., naltrexone). Preclinical studies of behavioral sequelae of such maintenance therapies may be useful in predicting behavioral and subjective effects of repeated opioid use in humans. The proposed projects will use drug discrimination assays and other behavioral assays as model systems to assess how pharmacological and behavioral factors modulate the development and expression of opioid tolerance and dependence during repeated treatment with clinically important opioid agonists. A primary goal during the upcoming period is to evaluate the hypothesis that abstinence precipitated by classical opioid antagonists in dependent organisms arises from inverse agonist actions, rather than from competitive antagonism, per se We will pay particular attention to the possibility that behavioral abstinence responses, as measured in free-operant, drug discrimination, and place conditioning assays, may represent uniquely sensitive indices of inverse agonist effects. Building on studies conducted during the previous award period, other experiments will evaluate whether the magnitude of dependence varies with the intrinsic efficacy of the agonist used to establish physical dependence Project 1 will define the doses, routes of administration, and pretreatment times over which compounds will function as antagonists of acute agonist actions of the classic ¿ agonists morphine and DAMGO. As controls for potential non-¿, or non-opioid, mechanisms in morphine dependence, key antagonists will be compared for their ability to alter effects of ? and ¿ opioid agonists and selected non-opioids. Project 2 will assess the ability of classical and putative neutral opioid antagonists to provoke abstinence in acutely and chronically dependent organisms, focusing on performance altering and discriminative stimulus effects. Project 3 will assess the ability of compounds to produce a functional up regulation of opioid receptors. In order to begin an initial characterization of the potential aversive actions of classical and putative neutral opioid antagonists, Project 4 will assess the ability of promising compounds to establish place aversions.

描述（由适用提供）：当前对人Ooid滥用的治疗方法纳入了各种慢性药物疗法，包括Metagadone维护和较新的疗法，从而增加了低有效的Ooid激动剂（例如丁丙诺啡）或OOID拮抗剂（例如Naltrexone）。这种维持疗法的行为后遗症的临床前研究可能有助于预测重复使用OID在人类中的行为和主观效应。拟议的项目将使用药物歧视评估和其他行为分析作为模型系统，以评估药物和行为因素如何调节阿片类药物耐受性的发育和表达，并在重复治疗中使用临床上重要的阿片类药物激动剂进行重复治疗。在接下来的一段时间内的主要目标是评估以下假说：依赖有机体中的古典阿片类药物的禁欲是由激动剂的逆行为而不是竞争性拮抗作用引起的，我们将特别关注行为戒除响应的可能性，因为在自由行，药物歧视和态度敏感的情况下，对行为的戒除响应均表现出敏感性，并不是在敏感的态度。在上一个奖项期间进行的研究的基础上，其他实验将评估用于建立身体依赖项目1的激动剂的内在有效性的依赖性变化是否会定义剂量，给药途径和预处理时间，而化合物在哪些化合物中将充当经典的emonist iconist动作的拮抗作用。作为潜在的非 - 或非阿片类药物的对照，吗啡依赖性的机制，将根据其改变影响的能力来比较关键的拮抗剂？和»阿片类药物激动剂和选定的非阿片类药物。项目2将评估经典和假定的中性阿片类药物拮抗剂在急性和长期依赖的生物中戒酒的能力，重点是改变性能和歧视性刺激作用。项目3将评估化合物产生正常受体调节的能力。为了开始对经典和假定的中性阿片类拮抗剂的潜在厌恶作用的初步表征，项目4将评估承诺化合物建立厌恶态度的能力。