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Original Article |
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Neuropsychopharmacology (2001) 25 213-223.10.1038/S0893-133X(01)00231-7
A Simple Method to Measure Baseline Occupancy of Neostriatal Dopamine D2 Receptors by Dopamine In Vivo in Healthy Subjects
NPLG Verhoeff MD, Ph.D, S Kapur MD, Ph.D, D Hussey BSc, M Lee BSc, B Christensen Ph.D, C Psych, G Papatheodorou MD and RB Zipursky MD |
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PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
Correspondence: Dr NPLG Verhoeff, Clinical Research Fellow Psychiatry, Centre for Addiction and Mental Health, Clarke Site, PET Centre, 250 College Street, Toronto, Ontario M5T 1R8, Canada
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ABSTRACT
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The effect of endogenous dopamine (DA) on measurement of neostriatal DA D2 receptor binding potential (D2RBP) in vivo was evaluated with positron emission tomography (PET) and the radiotracer [11C]raclopride by comparing the D2RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4.5 g  -methyl-para-tyrosine (AMPT) given in 25 h. Six healthy subjects completed the protocol. The AMPT treatment increased D2RBP significantly from 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 [11C]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.
Keywords: Dopamine; Dopamine D2 receptors; [11C]raclopride; Positron emission tomography; -methyl-para-tyrosine; In vivo binding |
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