Dopamine Receptors in Schizophrenia

Abstract

Schizophrenia is believed to involve altered dopaminergic transmission. This is supported by the fact that chronic use of dopamine agonists such as amphetamine can cause psychotic symptoms, and dopamine D2 receptor antagonists are the most widely used drugs for the treatment of schizophrenia. However, most of the in vivo imaging studies with drug-free or drug-naive patients could not detect a significant change in striatal D2 receptors ¹. On the other hand, neuropathological ² and neuroimaging studies have demonstrated abnormalities in the extrastriatal regions of schizophrenia. Dopamine receptors are classified into five subtypes, and selective ligands have been developed for D1 and D2 subtypes. In the cortical regions, the density of D1 receptor is higher than that of D2 receptor^{3, 4} . Dl receptor has been implicated in the control of working memory. We have recently reported the abnormality of dopamine D1 receptor binding in the prefrontal cortex of patients with schizophrenia, and its relation to negative symptoms and poor performance in the Wisconsin Card Sorting Test⁵. On the other hand, an increasing body of evidence favors a crucial role of extrastriatal regions in the pathophysiology of positive symptoms, and the extrastriatal D2 receptor is expected to be the common site of action of antipsychotics ⁶. We found that extrastriatal dopamine D2 receptor was the site of antipsychotic drug action ⁷. However, unexpectedly, reduced D2 receptor binding was observed in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D2 receptor binding and the positive symptom score on Brief Psychiatric Rating Scale (BPRS) ⁸.