title: Imaging D2 receptor occupancy by endogenous dopamine in humans.
abstract: The impact of endogenous dopamine on in vivo measurement of D2 receptors in humans was evaluated with single photon emission computerized tomography (SPECT) by comparing the binding potential (BP) of the selective D2 radiotracer [123I]IBZM before and after acute dopamine depletion. Dopamine depletion was achieved by administration of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT), given orally at a dose of 1 g every six hours for two days. AMPT increased [123I]IBZM BP by 28 +/- 16% (+/- SD, n = 9). Experiments in rodents suggested that this effect was due to removal of endogenous dopamine rather than D2 receptor upregulation. Synaptic dopamine concentration was estimated as 45 +/- 25 nM, in agreement with values reported in rodents. The amplitude and the variability of the AMPT effect suggested that competition by endogenous dopamine introduces a significant error in measurement of D2 receptors in vivo with positron emission tomography (PET) or SPECT. However, these results also imply that D2 receptor imaging coupled with acute dopamine depletion might provide estimates of synaptic dopamine concentration in the living human brain.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Laruelle
authors.forename: C D
authors.initials: CD
authors.lastname: D'Souza
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: A
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: S J
authors.initials: SJ
authors.lastname: Kanes
authors.forename: C L
authors.initials: CL
authors.lastname: Fingado
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: M B
authors.initials: MB
authors.lastname: Bowers
authors.forename: P
authors.initials: P
authors.lastname: Jatlow
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000818:Animals; D001549:Benzamides; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011759:Pyrrolidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D019805:alpha-Methyltyrosine / Q000097:blood / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid