Dopamine receptors are really interesting. They're targets for most commonly administered second generation antipsychotics (SGAs), and the canon has been that block of dopamine receptor-dependent signaling is the primary way in which SGAs help with neuropsychiatric symptoms. But here, by examining a non-canonical siganling pathway in the axon initial segment, Selin Schamiloglu, shows that some SGAs can act as agonists, provided that signaling occurs through arrestin instead of G-protein. Then, a collaboration with friends in the Whistler lab at UC Davis, Elinor Lewis, and Anne Hergarden, further show that this signaling might be important for regulating receptor expression on the cell surface, and aspects of drug tolerance over time. This reveals a very different way of thinking about SGA action, which we hope to continue to examine to see whether these are features that should be examined more as new drugs reach the market.