Neurovascular coupling of striatal dopamine D2/3 receptor availability and perfusion using simultaneous PET/MR in humans.

Abstract

The midbrain dopamine system contributes to important neural functions in the basal ganglia, and is involved in aspects of pathological processes in schizophrenia. In preclinical and clinical studies, pharmacological blockade or stimulation of brain dopamine receptors alters cerebral perfusion, which is a surrogate marker of metabolic activity. However, there is scant documentation of this neurofunctional coupling in relation to individual differences in the dopamine system of healthy humans. We therefore tested the hypothesis that baseline dopamine D2/3 receptor availability predicts individual blood flow responses to challenge with a dopamine agonist. We used [18F]fallypride positron emission tomography (PET) imaging to quantify dopamine D2/3 receptor availability as binding potential (BPND) in nine healthy subjects. Using simultaneous perfusion-weighted functional magnetic resonance imaging (fMRI), we measured perfusion at baseline and after challenge with the dopamine agonist apomorphine. Results of this multimodal imaging study revealed a strong negative association between baseline D2/3 dopamine receptor availability and apomorphine-induced perfusion changes in the human basal ganglia. There was considerable intra-individual variation in the neurovascular response to the apomorphine challenge, which may call for further investigation of the dopaminergic regulation of cerebral perfusion in patients with schizophrenia. This study describes a novel paradigm for assessing dopamine sensitivity, facilitating an exploration of the dopamine supersensitivity hypothesis.