The Role of Extrastriatal Dopamine D2 Receptors in Schizophrenia

Despite numerous studies on extrastriatal regions involved in schizophrenia, studies on the functional implications of dopamine (DA) D2 receptors in the extrastriatal regions, including the cortex and thalamus, are limited. We review postmortem and in vivo human imaging studies as well as animal studies, focusing on the function of extrastriatal DA D2 receptors and their role in the pathophysiology of schizophrenia. Based on recent findings, cortical DA D2 receptors may interact with the gamma-aminobutyric acid system to modulate DA transmission, and thalamic DA D2 receptors are likely to participate in sensory gating function into the prefrontal cortex. We have found decreased DA D2 receptors in the anterior cingulate cortex and thalamic subregions of patients with schizophrenia. These observations may suggest that alterations of extrastriatal DA D2 receptors are involved in dysregulation of DA transmission and sensory signals from the thalamus to the cortex. Excessive excitatory signals from the thalamus might flow into the cortical neurotransmission system, aggravating dysregulation of DA transmission in both the striatal and extrastriatal regions in schizophrenia. These notions suggest the need for future investigations of extrastriatal DA D2 receptor function to gain important clues regarding the pathogenesis and of possible treatments for schizophrenia.