Time-dependent assessment of stimulus-evoked regional dopamine release

Rachel N. Lippert, Anna Lena Cremer, Sharmili Edwin Thanarajah, Clio Korn, Thomas Jahans-Price, Lauren M. Burgeno, Marc Tittgemeyer, Jens C. Brüning, Mark E. Walton and Heiko Backes ()
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Rachel N. Lippert: Max Planck Institute for Metabolism Research
Anna Lena Cremer: Max Planck Institute for Metabolism Research
Sharmili Edwin Thanarajah: Max Planck Institute for Metabolism Research
Clio Korn: University of Oxford, Warneford Hospital
Thomas Jahans-Price: University of Oxford
Lauren M. Burgeno: University of Oxford
Marc Tittgemeyer: Max Planck Institute for Metabolism Research
Jens C. Brüning: Max Planck Institute for Metabolism Research
Mark E. Walton: University of Oxford
Heiko Backes: Max Planck Institute for Metabolism Research

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract To date, the spatiotemporal release of specific neurotransmitters at physiological levels in the human brain cannot be detected. Here, we present a method that relates minute-by-minute fluctuations of the positron emission tomography (PET) radioligand [11C]raclopride directly to subsecond dopamine release events. We show theoretically that synaptic dopamine release induces low frequency temporal variations of extrasynaptic extracellular dopamine levels, at time scales of one minute, that can evoke detectable temporal variations in the [11C]raclopride signal. Hence, dopaminergic activity can be monitored via temporal fluctuations in the [11C]raclopride PET signal. We validate this theory using fast-scan cyclic voltammetry and [11C]raclopride PET in mice during chemogenetic activation of dopaminergic neurons. We then apply the method to data from human subjects given a palatable milkshake and discover immediate and—for the first time—delayed food-induced dopamine release. This method enables time-dependent regional monitoring of stimulus-evoked dopamine release at physiological levels.

Date: 2019
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DOI: 10.1038/s41467-018-08143-4

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