Neurobehavioral Effects of MDMA in Adolescent Monkeys

描述(由申请人提供)：青少年使用摇头丸(摇头丸)在美国是一个严重的健康问题。人类临床研究表明，长期使用MDMA会导致认知障碍和情绪改变，这可能表明存在神经毒性。然而，由于这些研究固有的局限性，需要一个合适的动物模型来确定在青春期反复接触MDMA对神经行为的影响。已经开发出使用超高场磁共振成像来跟踪猴子大脑神经生物学的全球变化的技术和方法。由于MRI是一种非侵入性技术，因此有可能进行前瞻性研究，跟踪同一受试者一生中大脑结构、功能和化学成分的发育变化。为此，将对在自然家庭环境中饲养的双胞胎青少年绒猴进行研究。其中一对双胞胎将按照青少年使用的间歇性时间表接触口服MDMA。另一对双胞胎将作为对照。动物从青春期到成年期将被定期成像，以评估神经生物学的发育变化。这些成像过程将与一系列行为和认知测试相协调，以评估心理社会发展、学习和记忆方面的变化。5-羟色胺能和多巴胺能神经传递的药理学挑战和神经化学研究将用于评估药物引起的神经毒性。这项工作的目标是更好地了解青少年接触MDMA对大脑功能、心理社会和认知发展的风险。

DESCRIPTION (provided by applicant): Adolescent use of MDMA ("Ecstasy") is a significant health problem in the United States. Human clinical studies suggest that chronic MDMA use leads to cognitive deficits and mood alterations that may be indicative of neurotoxicity. However, due to the limitations inherent in such studies, an appropriate animal model is needed to determine the neurobehavioral effects of repeated MDMA exposure during the adolescent period of development. Technology and methods have been developed for following global changes in brain neurobiology in monkeys using ultra-high field magnetic resonance imaging. Since MRI is a noninvasive technique it is possible to do prospective studies to follow developmental changes in brain structure, function and chemistry in the same subjects over the course of their lives. To this end, studies will be done on twin, adolescent marmoset monkeys, raised in their natural family environments. One twin will be exposed to oral MDMA at an intermittent schedule mirroring teenage use. The other twin will serve as a control. Animals will be periodically imaged from adolescence into adulthood to evaluate developmental changes in neurobiology. These imaging sessions will be coordinated with a series of behavioral and cognitive tests to evaluate changes in psychosocial development, learning and memory. Pharmacologic challenges and neurochemical studies on serotonergic and dopaminergic neurotransmission will be used to assess drug-induced neurotoxicity. The goal of this work is to better understand the risks of adolescent MDMA exposure on brain function, psychosocial and cognitive development.