Drug Self Administration and Withdrawal Effects on Cognitive Function

药物自我给药和停药对认知功能的影响

• 批准号: 8676769
• 负责人: Brian D. Kangas
• 金额: $ 14.85万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8676769
• 关键词: Abstinence; Address; Adverse effects; Animals; Area; Behavior; Behavioral; Biological Assay; Cannabinoids; Cannabis; Catheters; Cognition; Cognitive; Complex; Decision Making; Dependence; Discrimination; Drug Addiction; Drug Design; Exercise; Familiarity; Food; Funding Mechanisms; Goals; Hospitals; Impaired cognition; Implant; Individual; Intravenous; Knowledge; Laboratories; Laboratory Animals; Learning; Long-Term Effects; Marijuana; Memory; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Morphine; Naltrexone; National Institute of Drug Abuse; Operative Surgical Procedures; Opioid; Opioid Analgesics; Oxycodone; Performance; Pharmaceutical Preparations; Pharmacology; Physical Dependence; Principal Investigator; Procedures; Public Health; Qualifying; Reinforcement Schedule; Research; Research Personnel; Research Training; Saimiri; Sampling; Schedule; Scientific Advances and Accomplishments; Scientist; Self Administration; Self-Administered; Supervision; Tetrahydrocannabinol; Time; Training; Training Programs; Withdrawal; Work; addiction; base; behavioral pharmacology; career; cognitive function; design; experience; investigator training; man; medical schools; neurobehavioral; nonhuman primate; novel; pre-clinical; prescription opioid; programs; public health relevance; reinforcer; rimonabant; skills; tool; touchscreen; translational study

DESCRIPTION (provided by applicant): Intravenous (IV) drug self-administration procedures in nonhuman primates (NHP) provide powerful laboratory tools with which to study persistent drug taking behavior and its neurobehavioral consequences. The present K01 application is designed to obtain support and "protected time" for Dr. Brian Kangas (Principal Investigator) to gain training and experience in conducting NHP self-administration studies. This training will advance his scientific career goals and also address the need for new young investigators experienced in this methodology. The Principal Investigator will apply his newly-developed expertise to examine the potentially adverse effects of two self-administered drugs that have high dependence and abuse liability (tetrahydrocannabinol [9-THC], the active ingredient in marijuana, and oxycodone, and the prescription opioid analgesic) on different aspects of cognition. In this project, the Principal Investigator first will complete an intensive training program in IV self-administration methodology at McLean Hospital/Harvard Medical School under the mentorship of Dr. J. Bergman, who is internationally recognized for his IV self-administration work in NHP. This training will include conceptual and practical aspects of self- administration methodology. The Principal Investigator will become skilled in the surgical/technical skills needed to implant and maintain IV catheters over long periods of time (e.g., 2-3 years). In addition, training during daily ongoing studies of oxycodone's reinforcing effects will provide familiarity with technical, behavioral, and tactical issues that arise during V self-administration studies, and decision-making strategies to efficiently achieve research goals. Second, the Principal Investigator will receive advanced training in cannabinoid self-administration to learn the technical and behavioral skills that facilitate studies with drugs that are less readily established as reinforcers in laboratory animals. This training will occur under Dr. S.R. Goldberg's co-mentorship in his laboratory at NIDA/IRP, where he has pioneered, replicated, and expanded these efforts over the last 12 years. Third, the Principal Investigator will conduct studies of the effects of persistently self-administered oxycodone and 9-THC on cognition-related behavior by examining their impact in novel assays of learning and memory. Both oxycodone and 9-THC produce physical dependence and addiction, and present major public health concerns. Oxycodone is a more robust reinforcer than 9-THC but may have lesser effects on cognition; thus, the experience gained by studying both types of reinforcers will be an important feature of the Principal Investigator's training. Changes in cognitive-based performance also will be evaluated following treatment with the antagonist's naltrexone and rimonabant in, respectively, oxycodone- and 9-THC -maintained subjects and, as well, following the discontinuation of their IV self-administration for varying periods of abstinence. These studies will provide information on cognitive impairments that may attend self-administration of these drugs. This information is essential for understanding and eventually countering such effects in the treatment of drug addiction. Overall, this project will provide the Principal Investigator with a unique expertise and perspective for continuing research on the cognitive impact of drug addiction.

描述（由申请方提供）：非人灵长类动物（NHP）的静脉（IV）药物自我给药程序为研究持续用药行为及其神经行为后果提供了强大的实验室工具。本K 01申请旨在为Brian Kangas博士（主要研究者）获得支持和“保护时间”，以获得开展NHP自我给药研究的培训和经验。这项培训将推进他的科学职业目标，并解决对新的年轻研究人员在这种方法学方面的经验的需求。主要研究者将运用他新开发的专业知识来检查两种自我管理药物的潜在不良影响，这两种药物具有高度依赖性和滥用倾向（四氢大麻酚[9-THC]，大麻中的活性成分，羟考酮和处方阿片类镇痛药）对认知的不同方面。在本项目中，主要研究者将首先在姆克林医院/哈佛医学院完成IV自我给药方法的强化培训课程，并接受J. Bergman博士的指导，J. Bergman博士在NHP中的IV自我给药工作得到国际认可。这种培训将包括自我管理方法的概念和实践方面。主要研究者将熟练掌握长期植入和维护IV导管所需的手术/技术技能（例如，2-3年）。此外，在羟考酮强化作用的日常持续研究期间进行的培训将使患者熟悉V自我给药研究期间出现的技术、行为和战术问题，以及有效实现研究目标的决策策略。其次，主要研究者将接受大麻素自我给药的高级培训，以学习促进药物研究的技术和行为技能， 不太容易在实验室动物中建立作为免疫抑制剂。该培训将在S.R.博士的指导下进行。Goldberg在NIDA/IRP实验室的共同导师，在过去的12年里，他在那里开创、复制和扩展了这些努力。第三，主要研究者将通过检查羟考酮和9-THC在新型学习和记忆试验中的影响，研究持续自我给药羟考酮和9-THC对认知相关行为的影响。羟考酮和9-THC都会产生身体依赖和成瘾，并引起重大的公共卫生问题。羟考酮是一种比9-THC更稳健的兴奋剂，但对认知的影响可能较小;因此，通过研究两种类型兴奋剂获得的经验将是主要研究者培训的重要特征。还将在羟考酮和9-THC维持受试者中分别用拮抗剂的纳洛酮和利莫那班治疗后，以及在其IV自我给药停止不同戒断期后，评价基于认知的表现的变化。这些研究将提供关于可能伴随这些药物自我给药的认知障碍的信息。这一信息对于理解并最终在戒毒治疗中消除这种影响至关重要。总体而言，该项目将为主要研究者提供独特的专业知识和视角，以继续研究药物成瘾的认知影响。