Dopamine Synthesis Capacity is Associated with D2/3 Receptor Binding but Not Dopamine Release

Positron Emission Tomography (PET) imaging allows the estimation of multiple aspects of dopamine function including dopamine synthesis capacity, dopamine release, and D2/3 receptor binding. Though dopaminergic dysregulation characterizes a number of neuropsychiatric disorders including schizophrenia and addiction, there has been relatively little investigation into the nature of relationships across dopamine markers within healthy individuals. Here we used PET imaging in 40 healthy adults to compare, within individuals, the estimates of dopamine synthesis capacity (K_i) using 6-[¹⁸F]fluoro-l-m-tyrosine ([¹⁸F]FMT; a substrate for aromatic amino acid decarboxylase), baseline D2/3 receptor-binding potential using [¹¹C]raclopride (a weak competitive D2/3 receptor antagonist), and dopamine release using [¹¹C]raclopride paired with oral methylphenidate administration. Methylphenidate increases synaptic dopamine by blocking the dopamine transporter. We estimated dopamine release by contrasting baseline D2/3 receptor binding and D2/3 receptor binding following methylphenidate. Analysis of relationships among the three measurements within striatal regions of interest revealed a positive correlation between [¹⁸F]FMT K_i and the baseline (placebo) [¹¹C]raclopride measure, such that participants with greater synthesis capacity showed higher D2/3 receptor-binding potential. In contrast, there was no relationship between [¹⁸F]FMT and methylphenidate-induced [¹¹C]raclopride displacement. These findings shed light on the nature of regulation between pre- and postsynaptic dopamine function in healthy adults, which may serve as a template from which to identify and describe alteration with disease.