Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum

Biol Psychiatry. 2005 Mar 1;57(5):533-42. doi: 10.1016/j.biopsych.2004.11.036.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Blotting, Western / methods
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gene Expression Regulation / drug effects*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Immunohistochemistry / methods
  • Phosphorylation / drug effects
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Trans-Activators / metabolism*
  • beta Catenin


  • Antipsychotic Agents
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Glycogen Synthase Kinase 3