The dopamine hypothesis of schizophrenia has recently evolved into a model of dysfunctional integration between cortical and subcortical dopaminergic activity. Anatomical data suggest that regional alterations in dopaminergic activity may be linked by means of the rich glutamatergic innervation of the striatum by corticostriatal projections, suggesting a potential role for glutamatergic dysfunction in schizophrenia. Although pharmacological data have implicated the NMDA subtype of glutamate receptor in this illness, disturbance in AMPA receptor expression could potentially lead to the NMDA receptor hypoactivity hypothesized in schizophrenia. To address this possibility, we examined AMPA receptor binding and subunit mRNA levels in prefrontal cortex and striatum of schizophrenics and matched controls. There were no significant differences in AMPA receptor binding or subunit mRNA levels in either prefrontal cortical or striatal regions of schizophrenics. Furthermore, AMPA receptor expression did not seem to be regulated by chronic antipsychotic drug exposure, when neuroleptic treated and drug-free schizophrenics were analyzed separately. These data do not support a role for altered AMPA receptor expression in cortex and striatum in schizophrenia.
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