A Simple Method to Measure Baseline Occupancy of Neostriatal Dopamine D2 Receptors by Dopamine In Vivo in Healthy Subjects

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 25; no. 2; pp. 213 - 223
• Main Authors: Verhoeff, N.P.L.G, Kapur, S, Hussey, D, Lee, M, Christensen, B, C.Psych, Papatheodorou, G, Zipursky, R.B
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2001; Nature Publishing; Nature Publishing Group
• Subjects: [11C]raclopride; Adult; alpha-Methyltyrosine - pharmacology; Analysis of Variance; Biological and medical sciences; Cell receptors; Cell structures and functions; Cognition - drug effects; Cognition - physiology; Dopamine; Dopamine - metabolism; Dopamine Antagonists - metabolism; Dopamine D2 receptors; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Homovanillic Acid - blood; Humans; In vivo binding; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Mental health; Methoxyhydroxyphenylglycol - blood; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Neostriatum - diagnostic imaging; Neostriatum - drug effects; Neostriatum - metabolism; Nervous system; Outcome Assessment (Health Care); Positron emission tomography; Prolactin - blood; Raclopride - metabolism; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Receptors, Dopamine D2 - biosynthesis; Statistics, Nonparametric; Tomography; Tomography, Emission-Computed - methods; α-methyl-para-tyrosine; Toronto Ontario Canada; Canada; α-methyl-para-tyrosine; In vivo binding; Dopamine; Dopamine D2 receptors; [11C]raclopride; Positron emission tomography; Human; Healthy subject; Metabolite; Central nervous system; Molecular interaction; Corpus striatum; Catecholamine; Depletion; Analysis method; D2 Dopamine receptor; Investigation method; Medical imagery; Quantitative analysis; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(01)00231-7

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 α-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.