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Aripiprazole and haloperidol activate GSK3β-dependent signalling pathway differentially in various brain regions of rats
Illawarra Health and Medical Research Institute
  • Bo Pan, University of Wollongong
  • Xu-Feng Huang, University of Wollongong
  • Chao Deng, University of Wollongong
RIS ID
106608
Publication Details

Pan, B., Huang, X. & Deng, C. (2016). Aripiprazole and haloperidol activate GSK3β-dependent signalling pathway differentially in various brain regions of rats. International Journal of Molecular Sciences, 17 (4), 459-1 - 459-11.

Abstract
Aripiprazole, a dopamine D2 receptor (D2R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D2R antagonist) and bifeprunox (a D2R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D2Rs.
Grant Number
NHMRC/1008473
Citation Information
Bo Pan, Xu-Feng Huang and Chao Deng. "Aripiprazole and haloperidol activate GSK3β-dependent signalling pathway differentially in various brain regions of rats" (2016)
Available at: http://works.bepress.com/xhuang/169/