The effects of antipsychotics on β-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats
Article first published online: 2 SEP 2005
Journal of Neurochemistry
Volume 95, Issue 2, pages 513–525, October 2005
How to Cite
Alimohamad, H., Sutton, L., Mouyal, J., Rajakumar, N. and Rushlow, W. J. (2005), The effects of antipsychotics on β-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats. Journal of Neurochemistry, 95: 513–525. doi: 10.1111/j.1471-4159.2005.03388.x
- Issue published online: 12 SEP 2005
- Article first published online: 2 SEP 2005
- Received March 27, 2005; revised manuscript received June 7, 2005; accepted June 10, 2005.
- signal transduction;
- substantia nigra;
- ventral tegmental area;
Protein kinase B and glycogen synthase kinase-3 have been identified as susceptibility genes for schizophrenia and altered protein and mRNA levels have been detected in the brains of schizophrenics post-mortem. Recently, we reported that haloperidol, clozapine and risperidone alter glycogen synthase kinase-3 and β-catenin protein expression and glycogen synthase kinase-3 phosphorylation levels in the rat prefrontal cortex and striatum. In the current study, β-catenin, adenomatous polyposis coli, Wnt1, dishevelled and glycogen synthase kinase-3 were examined in the ventral midbrain and hippocampus using western blotting. In addition, β-catenin and GSK-3 were examined in the substantia nigra and ventral tegmental area using confocal and fluorescence microscopy. The results indicate that repeated antipsychotic administration results in significant elevations in glycogen synthase kinase-3, β-catenin and dishevelled-3 protein levels in the ventral midbrain and hippocampus. Raclopride causes similar changes in β-catenin and GSK-3 in the ventral midbrain, suggesting that D2 dopamine receptor antagonism mediated the changes observed following antipsychotic administration. In contrast, amphetamine, a drug capable of inducing psychotic episodes, had the opposite effect on β-catenin and GSK-3 in the ventral midbrain. Collectively, the results suggest that antipsychotics may exert their beneficial effects through modifications to proteins that are associated with the canonical Wnt pathway.