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Nowadays, whether people suffer from depression, mental health disorders, or addictions, medication can help. Researchers have learned how to fine tune the brain's functions, often by targeting chemicals called neurotransmitters and the many signaling pathways through which they act. Although certain neurotransmitters had been identified more than 40 years ago, scientists knew relatively little about how these chemicals actually functioned. The basis for much of what neuroscientists know today about brain signaling was shaped by National Academy of Sciences member Paul Greengard's 1972 PNAS Classic paper, “Dopamine-sensitive Adenylate cyclase in caudate nucleus of rat brain, and its similarity to the ‘dopamine receptor’” (1). In the PNAS Classic paper, Kebabian et al. (1) identified enzyme activity in the brain that was triggered by the neurotransmitter dopamine. This understanding of how dopamine works has formed our basic understanding of brain signaling and helped discover therapies for brain disorders. Dopamine continues to be the subject of much research and has been implicated in addictions, attention deficit hyperactivity disorder (ADHD), mood disorders, schizophrenia, and movement disorders such as Parkinson's disease. Greengard realized that the enzyme activity that he discovered probably indicated the presence of a dopamine receptor that bound to the neurotransmitter. Subsequent identification and purification of the proteins that form this receptor revealed that Greengard had figured out the critical first steps of neurotransmitter signaling. He went on to show that the receptor-mediated enzyme activates a second messenger, which then triggers a cascade of other signaling events that regulate complex neurological traits and affect how nerve cells grow and function. Dopamine's role as a neurotransmitter was first uncovered by Arvid Carlsson, who shared the 2000 Nobel Prize in Physiology and Medicine for this discovery (2–4). Carlsson et al. (2, 3) noticed that patients with Parkinson's disease have particularly low …

Paul Greengard: Signals underlying moods, addictions, and brain disorders