BACKGROUND: It has been demonstrated that schizophrenics have altered levels and/or phosphorylation states of several Wnt related proteins in the brain, including beta-catenin and GSK-3, and may represent susceptibility loci for schizophrenia. The current study was conducted to assess the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3. METHODS: Western blotting and immunocytochemistry were employed to investigate the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3 following acute, subchronic and chronic drug administration. Specificity of the response was tested using additional drugs such as fluoxetine, amphetamine and valproic acid. RESULTS: Significant increases in the levels of beta-catenin and glycogen synthase kinase-3 total protein were identified following administration of clozapine, haloperidol or risperidone. The phosphorylation state of GSK-3 was also increased but phosphorylated beta-catenin levels were unaffected. Other drug compounds, with the exception of raclopride, had no effect on either GSK-3 or beta-catenin protein levels or distribution. CONCLUSIONS: Targeting of beta-catenin and GSK-3 is a common feature of antipsychotics regardless of class and appears to be mediated by D(2) dopamine receptors. Therefore changes in beta-catenin and GSK-3 may represent one of the mechanisms through which antipsychotics are able to exert behavioral changes.
BACKGROUND: It has been demonstrated that schizophrenics have altered levels and/or phosphorylation states of several Wnt related proteins in the brain, including beta-catenin and GSK-3, and may represent susceptibility loci for schizophrenia. The current study was conducted to assess the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3. METHODS: Western blotting and immunocytochemistry were employed to investigate the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3 following acute, subchronic and chronic drug administration. Specificity of the response was tested using additional drugs such as fluoxetine, amphetamine and valproic acid. RESULTS: Significant increases in the levels of beta-catenin and glycogen synthase kinase-3 total protein were identified following administration of clozapine, haloperidol or risperidone. The phosphorylation state of GSK-3 was also increased but phosphorylated beta-catenin levels were unaffected. Other drug compounds, with the exception of raclopride, had no effect on either GSK-3 or beta-catenin protein levels or distribution. CONCLUSIONS: Targeting of beta-catenin and GSK-3 is a common feature of antipsychotics regardless of class and appears to be mediated by D(2) dopamine receptors. Therefore changes in beta-catenin and GSK-3 may represent one of the mechanisms through which antipsychotics are able to exert behavioral changes.
Authors: Marta De Felice; Justine Renard; Roger Hudson; Hanna J Szkudlarek; Brian J Pereira; Susanne Schmid; Walter J Rushlow; Steven R Laviolette Journal: J Neurosci Date: 2020-12-02 Impact factor: 6.167
Authors: Jeffrey A Lieberman; Frank P Bymaster; Herbert Y Meltzer; Ariel Y Deutch; Gary E Duncan; Christine E Marx; June R Aprille; Donard S Dwyer; Xin-Min Li; Sahebarao P Mahadik; Ronald S Duman; Joseph H Porter; Josephine S Modica-Napolitano; Samuel S Newton; John G Csernansky Journal: Pharmacol Rev Date: 2008-09 Impact factor: 25.468
Authors: Bernard Masri; Ali Salahpour; Michael Didriksen; Valentina Ghisi; Jean-Martin Beaulieu; Raul R Gainetdinov; Marc G Caron Journal: Proc Natl Acad Sci U S A Date: 2008-09-03 Impact factor: 11.205