Genetic analysis of the effect of antipsychotic drugs on the Akt network. (A) DAF-2 is required for clozapine (CLO), olanzapine (OLA), and trifluoperazine (TRI) to block the nuclear accumulation of DAF-16::GFP. Serotonin (5-HT) served as a positive control. (B) AKT-1 is required for clozapine, olanzapine, and trifluoperazine to block the nuclear accumulation of DAF-16::GFP. (C) In an sgk-1(ok538) null background, clozapine did not block nuclear accumulation of DAF-16::GFP; however, olanzapine and trifluoperazine did. (D) In a tph-1(mg280) null background, antipsychotic drugs are slightly less effective at blocking the nuclear accumulation of DAF-16::GFP. (E) In a sek-1(km4) null background, clozapine, olanzapine, and trifluoperazine blocked the nuclear accumulation of DAF-16::GFP indicating that these drugs do not require SEK-1. (F and G) In the tax-6(p675) strong loss of function mutant or cnb-1(jh103) null backgrounds, clozapine, olanzapine, and trifluoperazine blocked the nuclear accumulation of DAF-16::GFP. tax-6 encodes the calcineurin catalytic domain, and cnb-1 encodes the calcineurin regulatory domain (for each condition, n = 20; two tailed Student’s t-test, *P < 0.05, **P < 0.01 mean ± SEM compared to those of DMSO-treated WT animals; #P < 0.05, ##P < 0.01 mean ± SEM compared to those of DMSO-treated mutants).