This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In animals, methamphetamine is a documented dopamine (DA) neurotoxin. Whether methamphetamine is also neurotoxic in humans has not been determined, largely because of the difficulty in assessing dopamine neuronal integrity in the living human brain. Positron emission tomography (PET), when used in conjunction with neuron specific ligands, is a non-invasive imaging technique that can be used to study brain DA neurons in living humans. For example, PET imaging with [11C]WIN-35,428 and/or [11C]DTBZ has recently facilitated the successful detection of DA neuron damage in patients with mild Parkinson's disease, a neurodegenerative condition characterized by degeneration of brain DA neurons. The overall goal of the present project is to use PET imaging with [11C]WIN-35,428 and [11C]DTBZ, in conjunction with pharmacologic challenge studies using the DA-depleting agent alpha-methyl-paratyrosine (AMPT), to ascertain whether humans previously exposed to high doses of methamphetamine show evidence of dopaminergic neuronal injury. In addition to the PET scans and pharmacological challenge with AMPT, all subjects will undergo routine medical, psychological, and laboratory evaluation, including a detailed physical and neurological examination, and a structured psychiatric interview using the Scheduled Interview for DSM-IV. The long-term goal of the project is to better delineate the public health risks/consequences of recreational methamphetamine exposure.
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