On the basis of impaired glutamatergic transmission and the potential role of astrocytes in schizophrenia, we treated cultured astrocytes with MK-801, an NMDA-receptor antagonist, to investigate whether the resulting proteome changes are similar to those we found in our earlier proteome analysis of schizophrenia human brain tissue as well as to better comprehend the role of astrocytes in the disorder. Indeed, there are similarities. Furthermore, to verify the efficacy of clozapine and its effect over the proteome, we treated MK-801-treated astrocytes with clozapine. Interestingly, clozapine reversed protein changes induced by MK-801. The treatment of cell cultures with neural transmission agonists and antagonists might provide useful insights about psychiatric disorders.