Differential associations of dopamine synthesis capacity with the dopamine transporter and D2 receptor availability as assessed by PET in the living human brain

Background: The dopamine (DA) neurotransmission has been implicated in fundamental brain functions, exemplified by movement controls, reward-seeking, motivation, and cognition. Although dysregulation of DA neurotransmission in the striatum is known to be involved in diverse neuropsychiatric disorders, it is yet to be clarified whether components of the DA transmission, such as synthesis, receptors, and reuptake are coupled with each other to homeostatically maintain the DA neurotransmission. The purpose of this study was to investigate associations of the DA synthesis capacity with the availabilities of DA transporters and D2 receptors in the striatum of healthy subjects. Methods: First, we examined correlations between the DA synthesis capacity and DA transporter availability in the caudate and putamen using PET data with L-[β-¹¹C]DOPA and [¹⁸F]FE-PE2I, respectively, acquired from our past dual-tracer studies. Next, we investigated relationships between the DA synthesis capacity and D2 receptor availability employing PET data with L-[β-¹¹C]DOPA and [¹¹C]raclopride, respectively, obtained from other previous dual-tracer assays. Results: We found a significant positive correlation between the DA synthesis capacity and DA transporter availability in the putamen, while no significant correlations between the DA synthesis capacity and D2 receptor availability in the striatum. Conclusion: The intimate association of the DA synthesis rate with the presynaptic reuptake of DA indicates homeostatic maintenance of the baseline synaptic DA concentration. In contrast, the total abundance of D2 receptors, which consist of presynaptic autoreceptors and postsynaptic modulatory receptors, may not have an immediate relationship to this regulatory mechanism.