Neurobehavioral Effects of MDMA in Adolescent Monkeys

描述（由申请人提供）：青少年使用MDMA（“摇头丸”）在美国是一个重大的健康问题。人类临床研究表明，长期使用MDMA会导致认知缺陷和情绪改变，这可能是神经毒性的指示。然而，由于此类研究固有的局限性，需要一个合适的动物模型来确定青春期发育期间反复暴露于MDMA的神经行为影响。使用超高场磁共振成像技术和方法来跟踪猴子大脑神经生物学的整体变化已经发展起来。由于核磁共振成像是一种非侵入性技术，因此可以进行前瞻性研究，跟踪同一受试者一生中大脑结构、功能和化学的发育变化。为此，将对在自然家庭环境中长大的双胞胎、青春期狨猴进行研究。其中一个双胞胎将以间歇性的时间表暴露于口服MDMA，反映青少年的使用情况。另一个双胞胎将作为对照。动物将从青春期到成年期定期成像，以评估神经生物学的发育变化。这些成像会议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诱导的神经毒性。这项工作的目的是为了更好地了解青少年接触MDMA对大脑功能、社会心理和认知发展的风险。

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.