Neurobehavioral Effects of MDMA in Adolescent Monkeys

描述（由申请人提供）：在美国，青少年使用MDMA（“摇头丸”）是一个严重的健康问题。 人类临床研究表明，长期使用MDMA会导致认知缺陷和情绪改变，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，需要一个适当的动物模型来确定在青春期发育期间反复暴露于MDMA的神经行为影响。 已经开发了用于使用超高场磁共振成像来跟踪猴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，因此可以进行前瞻性研究，以跟踪同一受试者在其生命过程中大脑结构，功能和化学的发展变化。 为此，将对在自然家庭环境中长大的双胞胎青春期绒猴进行研究。 双胞胎中的一个将以间歇性的时间表暴露于口服MDMA，这反映了青少年的使用。 另一个双胞胎将作为对照。 从青春期到成年期，将定期对动物进行成像，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，学习和记忆的变化。 将使用对多巴胺能和多巴胺能神经传递的药理学挑战和神经化学研究来评估药物诱导的神经毒性。 这项工作的目标是更好地了解青少年MDMA暴露对大脑功能，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.