Brain imaging and cognitive effects of cocaine self-administration in monkeys

猴子自我注射可卡因的脑成像和认知效应

• 批准号: 7867262
• 负责人: Paul W. Czoty
• 金额: $ 21.59万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7867262
• 关键词: Abstinence; Animal Model; Animals; Applications Grants; Area; Award; Behavioral; Brain; Brain imaging; Brain region; Chronic; Cocaine; Cocaine Abuse; Cocaine Dependence; Cocaine Users; Cognition; Cognitive; Data; Dependence; Deterioration; Development; Diffusion Magnetic Resonance Imaging; Drug abuse; Drug usage; Female; Future; Goals; Health; Human; Image; Imaging Techniques; Imaging technology; Impaired cognition; Individual; Long-Term Effects; Longitudinal Studies; Macaca fascicularis; Magnetic Resonance Spectroscopy; Metabolic; Modeling; Monkeys; National Institute of Drug Abuse; Neurobiology; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Prefrontal Cortex; Procedures; Public Health; Recovery; Reproducibility; Research; Sampling; Scanning; Self Administration; Self-Administered; Substance abuse problem; Task Performances; Temporal Lobe; Testing; Time; Training; addiction; brain behavior; career; cocaine exposure; cocaine use; cognitive function; effective therapy; experience; follow-up; human subject; nonhuman primate; novel strategies; programs; public health relevance; response; success; therapy development; time use; white matter

DESCRIPTION (provided by applicant): Although cocaine addiction persists as a major public health concern, effective medications are currently unavailable. Development of treatments for cocaine dependence will be aided by a more thorough understanding of the effects of long-term cocaine use on the brain and the impact of these changes on cognitive function. Studies using animal models with proven validity in drug abuse research will help achieve this goal. The primary aim of this 1-year grant proposal is to implement the brain imaging techniques diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) in monkeys to generate data to support more extensive future proposals. Additional aims are to document the effects of chronic cocaine self- administration on the brain and behavior in monkeys. To accomplish these aims, a DTI/MRS scan will be performed twice on eight female cynomolgus monkeys to establish appropriate test-retest validity (Specific Aim 1). Subsequently, monkeys will self-administer cocaine (6.0 mg/kg/day) for three months, at which time a follow-up DTI/MRS scan will be conducted. After this point, four monkeys will continue to self-administer cocaine while cocaine exposure is discontinued in the remaining four, and a final DTI/MRS scan will be conducted three months later (Specific Aim 2). In addition, cognitive function will be assessed every other week using a delayed match-to-sample task (Specific Aim 3). The overarching hypothesis is that progressive and parallel alterations will be observed in white matter integrity, neurometabolite concentrations and cognitive function during cocaine self-administration and abstinence that implicate specific brain regions and pathophysiological mechanisms in the cognitive decline observed after long-term cocaine use. Thus, in addition to providing data to support the establishment of the P.I.'s independent research career, results of the present studies will considerably enhance our understanding of the effects of chronic cocaine use, interpretation of imaging studies in human cocaine abusers, medications development, and, ultimately, treatment of cocaine dependence.

描述（由申请人提供）：虽然可卡因成瘾仍然是一个主要的公共卫生问题，但目前还没有有效的药物。更透彻地了解长期使用可卡因对大脑的影响以及这些变化对认知功能的影响，将有助于开发可卡因依赖的治疗方法。使用在药物滥用研究中已被证明有效的动物模型进行研究将有助于实现这一目标。这项为期一年的拨款提案的主要目的是在猴子中实施脑成像技术扩散张量成像（DTI）和磁共振波谱（MRS），以生成数据来支持更广泛的未来提案。其他目的是记录慢性可卡因自我给药对猴子大脑和行为的影响。为实现这些目标，将对8只雌性食蟹猴进行两次DTI/MRS扫描，以确定适当的重测有效性（具体目标1）。随后，猴将自我给予可卡因（6.0 mg/kg/天）三个月，此时将进行随访DTI/MRS扫描。此后，四只猴子将继续自我施用可卡因，而其余四只则停止可卡因暴露，并将在三个月后进行最终的DTI/MRS扫描（具体目标2）。此外，将使用延迟匹配样本任务（具体目标3）每隔一周评估认知功能。总体假设是，在可卡因自我给药和戒断期间，将观察到白色物质完整性、神经代谢物浓度和认知功能的进行性和平行改变，这涉及长期使用可卡因后观察到的认知下降的特定脑区和病理生理机制。因此，除了提供数据以支持建立P.I.的独立研究生涯，目前的研究结果将大大提高我们对慢性可卡因使用的影响，解释人类可卡因滥用者的成像研究，药物开发，并最终治疗可卡因依赖的理解。