Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans

Molecular Psychiatry
Nicolaas P L G VerhoeffShitij Kapur

Abstract

The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4500 mg alpha-methyl-para-tyrosine (AMPT) given in the 25 h prior to [(11)C]SCH23390 PET and of 5250 mg AMPT given in the 29 h prior to [(11)C]raclopride PET. Six healthy subjects completed the protocol. The AMPT treatment decreased plasma levels of the DA metabolite homovanillic acid by 61 +/- 16% (4500 mg; average +/- standard deviation) and 62 +/- 17% (5250 mg), and levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol by 58 +/- 7% (4500 mg) and 66 +/- 5% (5250 mg). This AMPT treatment increased D(2)RBP significantly from 3.18 +/- 0.34 to 3.59 +/- 0.30 but no significant change was observed in D(1)RBP (1.64 +/- 0.24 pre AMPT vs 1.70 +/- 0.17 post AMPT). Thus, while DA depletion "uncovers" D(2)receptors, it does not do so for D(1) receptors. The implications of this finding for measuring endogenous DA and its...Continue Reading

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Citations

Dec 14, 2002·Pharmacology, Biochemistry, and Behavior·Nicolaas P L G VerhoeffShitij Kapur
Jul 27, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Erik BootThérèse van Amelsvoort
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