A simple method to measure baseline occupancy of neostriatal dopamine D-2 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 emi ssion tomography (PET) and the radiotracer [C-11]raclopride by comparing th e D2RBP before and after acute DA depletion. DA depletion was achieved by p er-oral administration of 4.5 g alpha -methyl-para-tyrosine (AMPT) given in 25 h. Six healthy subjects completed the protocol. The AMPT treatment incr eased D2RBP sign flcantlyfrom 3.11 +/-0.25 to 3.68 +/-0.23 and decreased pl asma 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 w ith increase in errors of commission from Conners' Continuous Performance T est. On AMPT, a significant decrease in subjective happiness scores was obs erved. The results imply that a noninvasive [C-11]raclopride PET protocol c oupled with relatively brief administration of a rather low total dose of A MPT resulted in measurable acute DA depletion that might provide estimates of synaptic neostriatal DA concentration. [Neuropsychopharmacology 25:213-2 23, 2001] (C) 2001 American College of Neuropsychopharmacology. Published b y Elsevier Science Inc.