Neurobehavioral Effects of MDMA in Adolescent Monkeys

MDMA 对青春期猴子神经行为的影响

• 批准号: 7119619
• 负责人: Craig F Ferris
• 金额: $ 55.99万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119619
• 关键词: 3,4 methylenedioxymethamphetamine; Callithricidae; animal developmental psychology; behavior test; behavioral /social science research tag; cognition; cortisol; developmental neurobiology; dopamine transporter; functional magnetic resonance imaging; juvenile animal; longitudinal animal study; neural transmission; neurochemistry; neuropharmacology; neurophysiology; neuropsychology; neurotoxicology; piperazines; postmortem; prolactin; psychopharmacology; serotonin transporter; social behavior; twin /multiplet

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.

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，长期使用摇头丸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，由于此类研究固有的局限性，需要合适的动物模型来确定青少年发育期间反复接触 MDMA 的神经行为影响。 已经开发出利用超高场磁共振成像跟踪猴子脑神经生物学全球变化的技术和方法。 由于 MRI 是一种无创技术，因此可以进行前瞻性研究，以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，研究人员将对在自然家庭环境中饲养的双胞胎、青春期狨猴进行研究。 双胞胎中的一名将按照青少年的使用情况，间歇性地接触口服 MDMA。 另一个双胞胎将作为对照。 动物从青春期到成年期将定期进行成像，以评估神经生物学的发育变化。 这些成像课程将与一系列行为和认知测试相结合，以评估心理社会发展、学习和记忆的变化。 关于血清素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 MDMA 暴露对大脑功能、心理社会和认知发展的风险。