title: A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects.
abstract: The effect of endogenous dopamine (DA) on measurement of neostriatal DA D(2) receptor binding potential (D(2)RBP) in vivo was evaluated with positron emission tomography (PET) and the radiotracer [11C]raclopride by comparing the D(2)RBP 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 D(2)RBP 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 D(2)RBP 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.
authors: PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
authors: N P
authors: NP
authors: Verhoeff
authors: S
authors: S
authors: Kapur
authors: D
authors: D
authors: Hussey
authors: M
authors: M
authors: Lee
authors: B
authors: B
authors: Christensen
authors: C Psych
authors: G
authors: G
authors: Papatheodorou
authors: R B
authors: RB
authors: Zipursky
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D011388:Prolactin / Q000097:blood; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D018709:Statistics, Nonparametric; D014055:Tomography, Emission-Computed / Q000379:methods; D019805:alpha-Methyltyrosine / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D020891:Raclopride; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D011388:Prolactin; D004298:Dopamine; D006719:Homovanillic Acid