A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects

The effect of endogenous dopamine (DA) on measurement Of neostriatal DA D-2 receptor binding potential (D2RBP) in vivo was evaluated with positron emission tomography (PET) and the radiotracer [C-11]raclopride by comparing the D2RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4.5 g alpha -methyl-para-tyrosine (AMPT) given in 25 h. Six healthy subjects completed the protocol. The AMPT treatment increased D2RBP sign flcantlyfrom 3.11 +/-0.25 to 3.68 +/-0.23 and decreased plasma levels of the DA metabolite homovanillic acid by 71 +/- 11% and levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol by 53 +/-7%. Increase in D2RBP correlated with decrease in attentiveness and with increase in errors of commission from Conners' Continuous Performance Test. On AMPT, a significant decrease in subjective happiness scores was observed. The results imply that a noninvasive [C-11]raclopride PET protocol coupled with relatively brief administration of a rather low total dose of AMPT resulted in measurable acute DA depletion that might provide estimates of synaptic neostriatal DA concentration. [Neuropsychopharmacology 25:213-223, 2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.