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Clozapine and lithium require Caenorhabditis elegans β‐arrestin and serum‐ and glucocorticoid‐inducible kinase to affect Daf‐16 (Foxo) localization

Numerous studies have implicated low levels of signaling in the Akt network with psychotic illnesses, and a growing body of literature has shown that all classes of antipsychotic drugs increase Akt signaling. The most clinically effective antipsychotic drug is clozapine. With Caenorhabditis elegans as a model system, this study demonstrates that clozapine is unique among antipsychotic drugs because it requires β‐arrestin and serum and glucocorticoid‐inducible kinase (SGK) in addition to Akt to suppress the nuclear localization of DAF‐16 (Forkhead box O [FOXO]). Lithium, a mood stabilizer often used to treat psychosis, also requires β‐arrestin and SGK to suppress the nuclear localization of DAF‐16. © 2011 Wiley‐Liss, Inc.