The chemical tools for imaging dopamine release

Dopamine is a modulatory neurotransmitter involved in learning, motor functions, and reward. Many neuropsychiatric disorders, including Parkinson's disease, autism, and schizophrenia, are associated with imbalances or dysfunction in the dopaminergic system. Yet, our understanding of these pervasive public health issues is limited by our ability to effectively image dopamine in humans, which has long been a goal for chemists and neuroscientists. The last two decades have witnessed the development of many molecules used to trace dopamine. We review the small molecules, nanoparticles, and protein sensors used with fluorescent microscopy/photometry, MRI, and PET that shape dopamine research today. None of these tools observe dopamine itself, but instead harness the biology of the dopamine system-its synthetic and metabolic pathways, synaptic vesicle cycle, and receptors-in elegant ways. Their advantages and weaknesses are covered here, along with recent examples and the chemistry and biology that allow them to function.