Imaging D-2 receptor occupancy by endogenous dopamine in humans

The impact of endogenous dopamine on in vivo measurement of D-2 receptors in humans was evaluated with single photon emission computerized tomography (SPECT), by comparing the binding potential (BP) of the selective D-2 radiotracer [I-123]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 [I-123]IBZM BP by 28 +/- 16% (+/-SD, n = 9). Experiments in rodents suggested that this effect was due to removal of endogenous dopamine rather than D-2 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 D-2 receptors in vivo with positron emission tomography (PET) or SPECT. However, these results also imply that D-2 receptor imaging coupled with acute dopamine depletion might provide estimates of synaptic dopamine concentration in the living human brain. (C) 1997 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.