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. 3, 4-methylenedioxymethamphetamine (MDMA, ecstasy) produces a broad spectrum of psychological effects and neurotoxicity to serotonin neurons, attributed to selective transport by the serotonin transporter (SERT) by serotonin neurons. MDMA effects on dopamine neurons remain controversial. The relevance of DAT to MDMA effects was reinforced by our demonstration that (3H)MDMA affinity for the human dopamine transporter (DAT) and SERT are similar. We conducted PET imaging of striatum DAT in monkeys treated acutely (1 mg/kg, n = 4) or repeatedly with MDMA (1.5 mg/kg, 18 doses in 4 months, n=4). Results: MDMA occupancy of the DAT, viewed with (11C)altropane, was inconclusive. In 2/4 rhesus monkeys, acute MDMA displaced Caltropane binding to occupy 30% of the DAT, but in 2/4 monkeys, (11C)altropane binding increased. Repeated with (11C)CFT, MDMA consistently increased DAT binding potential by 121 +/- 7.5% (n = 4). Repeated exposure of cynomolgus monkeys to MDMA resulted in an 18% decrease in DAT binding potential (p less than 0.03) two weeks after the last dose. Discussion: Conceivably, the increased DAT binding potential (6/8 experiments) after an acute dose of MDMA reflects increased availability of cell surface DAT or MDMA-induced release of the DAT imaging probe from other sites. The small but consistent loss of DAT binding potential following repeated exposure to MDMA may reflect loss of DA neurons, compensatory down-regulation of the DAT, or MDMA-induced DAT internalization. MDMA modulation of the DAT and DA neurons warrants further investigation.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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Special Emphasis Panel (ZRR1-CM-9 (01))
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Harvard University
Veterinary Sciences
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United States
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Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

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