Neurobehavioral Effects of MDMA in Adolescent Monkeys

MDMA 对青春期猴子神经行为的影响

• 批准号: 7541663
• 负责人: Craig F Ferris
• 金额: $ 54.71万
• 依托单位: NORTHEASTERN UNIVERSITY
• 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/7541663
• 关键词: Adolescence; Adolescent; Adolescent Behavior; Adult; Anatomy; Animal Model; Animals; Behavior; Behavioral; Biochemical; Boxing; Brain; Callithrix; Chemistry; Chronic; Clinical Research; Cognitive; Cognitive deficits; Development; Dose; Environment; Family; Female Adolescents; Global Change; Goals; Health; Human; Hydrocortisone; Image; In Vitro; Individual; Learning; Life; Magnetic Resonance Imaging; Measures; Memory; Methods; Monkeys; Neurobiology; Oral; Pharmaceutical Preparations; Plasma; Prolactin; Prospective Studies; Reporting; Risk; Sampling; Schedule; Score; Series; Structure; System; Techniques; Technology; Testing; Toxic effect; Twin Multiple Birth; United States; Wisconsin; Work; brain tissue; disturbance in affect; ecstasy; human study; m chlorophenylpiperazine; male; neurobehavioral; neurochemistry; neurotoxicity; neurotransmission; psychosocial; recreational drug use; wasting

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（“狂喜”）是一个重大的健康问题。 人类的临床研究表明，慢性MDMA使用会导致认知缺陷和情绪改变，这可能表明神经毒性。 但是，由于此类研究固有的局限性，需要适当的动物模型来确定青春期发展期间反复MDMA暴露的神经行为影响。 已经开发了技术和方法，用于遵循使用超高场磁共振成像的猴子脑神经生物学的全球变化。 由于MRI是一种无创技术，因此可以进行前瞻性研究，以遵循同一受试者在其一生中大脑结构，功能和化学的发展变化。 为此，将对在其自​​然家庭环境中提出的双胞胎，青春期的果酱猴子进行研究。 一个双胞胎将在间歇时间镜像青少年使用的时间表上暴露于口服MDMA。 另一个双胞胎将用作控制。 从青春期到成年期，动物将定期成像，以评估神经生物学的发育变化。 这些成像会议将与一系列的行为和认知测试协调，以评估社会心理发展，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。 这项工作的目的是更好地了解青少年MDMA暴露于大脑功能，社会心理和认知发展的风险。