Abstract
The impact of endogenous dopamine on in vivo measurement of D2 receptors in humans was evaluated with single photon emission computerized tomography (SPECT), by comparing the binding potential (BP) of the selective D2 radiotracer [123I]IBZM before and after acute dopamine depletion. Dopamine depletion was achieved by administration of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT), given orally at a dose of 1 g every six hours for two days. AMPT increased [123I]IBZM BP by 28 ± 16% (±SD, n = 9). Experiments in rodents suggested that this effect was due to removal of endogenous dopamine rather than D2 receptor upregulation. Synaptic dopamine concentration was estimated as 45 ± 25 nM, in agreement with values reported in rodents. The amplitude and the variability of the AMPT effect suggested that competition by endogenous dopamine introduces a significant error in measurement of D2 receptors in vivo with positron emission tomography (PET) or SPECT. However, these results also imply that D2 receptor imaging coupled with acute dopamine depletion might provide estimates of synaptic dopamine concentration in the living human brain.
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Acknowledgements
We thank the subjects who participated in this study; Sue Giddings for performing the in vitro binding experiments; Harold Landis and Robert Reynolds for HVA and MHPG measurements; Ariel Talmor for AMPT measurements; Melyssa K. Madrak, Morgan Stratton, Yolanda Zea-Ponce, Ph.D., for radiochemistry procedures; Donna M. Damon for clinical ratings; Richard Weiss for data processing; Lynn Pantages-Torok for image analysis; Paul B. Hoffer, M.D., and Nallakkandra Rajeevan, Ph.D. for Nuclear Medicine expertise; Steven P. Ellis, Ph.D. for statistical analysis; the technologist staff of the NeuroSPECT laboratory at Yale/New Haven Hospital. Supported by the Scottish Rite Schizophrenia Research Program, the Department of Veterans Affairs (Schizophrenia Research Center) and the Public Health Service (Yale Mental Health Clinical Research Center).
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Laruelle, M., D’Souza, C., Baldwin, R. et al. Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans. Neuropsychopharmacol 17, 162–174 (1997). https://doi.org/10.1016/S0893-133X(97)00043-2
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DOI: https://doi.org/10.1016/S0893-133X(97)00043-2
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