The results of the current study showed that aripiprazole had similar effects on PKA subunits to haloperidol, but not bifeprunox in the CPu and VTA, indicating that relatively lower intrinsic activity of aripiprazole on D2R might be the mechanism of aripiprazole to exert its therapeutic effects on treating positive symptoms of schizophrenia; on the other hand, aripiprazole displayed a very different action mode on the GSK3β activity from the other two chemicals, probably explaining its therapeutic effects on both positive and negative symptoms of schizophrenia, with reduced EPS. Here, GSK3B is linked to schizophrenia.