Differential expression profiling of the synaptosome proteome in a rat model of antipsychotic resistance

This study used a comparative proteomics approach to identify the effects of the antipsychotic drugs, Chlorpromazine (CPZ), Clozapine (CLZ), and Quetiapine (QTP) on the synaptosomal protein of the cerebral cortex of Sprague-Dawley (SD) rats. The multivariate statistical test partial least squares - discriminant analysis (PLS-DA) was applied to build the models for screening out the variable important plot (VIP). The PLS-DA models were able to distinguish each drug treatment group and the control group; more importantly, the univariate differentially expressed protein spots were capable of being verified by the VIP of the models. The inter-relation ships among the identified proteins were analyzed using Pearson's correlation analysis and pathway analysis. Through the synaptosome proteome experiments, we established that the energy production of the mitochondrial function and 'Glycolysis/Gluconeogenesis' were involved in the response to antipsychotic medications. Furthermore, the G protein-coupled signal transduction system was also inhibited by antipsychotic medications. The result of our study should contribute to the understanding of the effects of antipsychotic drugs on synaptic function. (C) 2009 Elsevier B.V. All rights reserved.