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 (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.
Verhoeff
N P
NP
PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
Kapur
S
S
Hussey
D
D
Lee
M
M
Christensen
B
B
C Psych
Papatheodorou
G
G
Zipursky
R B
RB
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*
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D020891:Raclopride; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D011388:Prolactin; D004298:Dopamine; D006719:Homovanillic Acid