Dopamine depletion results in increased neostriatal D2, but not D1, receptor binding in humans

The effect of endogenous dopamine (DA) on neostriatal DA D-1 and D-2 receptor binding potentials (D1RBP and D2RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [C-11]SCH23390 and [(11)]raclopride, respectively, by comparing the D1RBP and D2RBP 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 [C-11]SCH23390 PET and of 5250 mg AMPT given in the 29 h prior to [11C]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 D2RBP significantly from 3.18 +/- 0.34 to 3.59 +/- 0.30 but no significant change was observed in D1RBP (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 effects on in vivo receptor binding in humans are discussed.