Exploring occupancy of dopamine D3 receptor by buspirone in humans using positron

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DESCRIPTION (provided by applicant): Drug addiction is a US public health and safety concern, urging improved treatment approaches such as targeted pharmacotherapies. Preclinical data have provided evidence that dopamine D3 receptor (DRD3) antagonism decreases addiction-relevant behaviour. Buspirone is an FDA-approved anxiolytic which acts as a serotonin partial agonist but has been recently identified as a DRD3 antagonist. Imaging with positron emission tomography (PET) permits the measurement of neurochemicals in vivo. PET has become a powerful tool for neuroscientists to visualize and localize receptors and estimate receptor occupancy by drug ligands. The process of imaging requires the injection of a positron-emitting radiotracer (e.g. [11C]-(+)-PHNO) that binds to the protein of interest (e.g. dopamine D3 receptors) followed by the measurement of this binding using the PET scanner. [11C]-(+)-PHNO is the only ligand allowing to measure dopamine D3 receptors occupancy in humans. Here, we will determine if buspirone significantly occupies the DRD3 at therapeutic doses in humans. These studies will allow for the translation of basic science discoveries into clinical validation. Our long term goal will be to determine the possible use of buspirone as an intervention for tobacco dependence. PUBLIC HEALTH RELEVANCE: Buspirone is an FDA-approved anxiolytic which acts as a serotonin partial agonist but has been recently identified as a dopamine D3 antagonist. Furthermore, recent brain imaging approaches have been developed allowing to measure dopamine D3 receptors in humans. The present project will determine the dose-occupancy relationship of buspirone for the dopamine D3 receptor in humans.