Neurobehavioral Effects of MDMA in Adolescent Monkeys

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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.