PET imaging of dopamine-D2 receptor internalization in schizophrenia

Molecular Psychiatry
J J WeinsteinAnissa Abi-Dargham

Abstract

Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R. Here we used 'late-phase' imaging after challenge to test the hypothesis that impaired D2R internalization in SZ leads to blunted late-phase displacement, or a faster return to baseline, in patients compared with healthy controls (HCs). We imaged 10 patients with SZ and 9 HCs with PET and [11C]raclopride at baseline and two times (3-5 and 6-10 h) following 0.5 mg kg-1 dextroamphetamine. We measured binding potential relative to non-displaceable compartment (BPND) and derived percent reduction from baseline (ΔBPND) for each postamphetamine scan. To test the hypothesis that time course of return of striatal BPND to baseline differed between SZ and HCs, we implemented a linear model with ΔBPND as depe...Continue Reading

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Citations

Feb 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Agnieszka KotarskaMelitta Schachner
Apr 17, 2019·International Journal of Molecular Sciences·Elise WoutersChristophe Stove
May 11, 2021·Journal of Magnetic Resonance Imaging : JMRI·Mario Serrano-SosaChuan Huang
Jul 21, 2021·Journal of Neural Engineering·Hung-Yun LuSamantha R Santacruz

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