Imaging studies - differential action of typical and atypical antipsychotics in a network perspective

Dopamine transmission remains central to our understanding of neurocircuitry models of schizophrenia, and to the mechanism of action of typical antipsychotic medications, which preferentially block D (2)-receptors in striatum. In cerebral cortex, D (2)- and D (1)- mediated transmission modulates information processing, and tunes the activity of the cortico-striato-thalamic loops, in which dopaminergic, glutamatergic, GABAergic and serotonergic projections are integrated and interconnected. Molecular imaging techniques, especially positron emission tomography, have been used to investigate the spatial pattern of the binding properties of antipsychotic medications. We now summarize the state of development of molecular imaging, integrated into a model of schizophrenia emphasizing dysfunction of a complex loop, rather than a discrete abnormality in the basal ganglia, as had been implicitly assumed in the classic dopamine model of psychosis. Finally, hypotheses are proposed to explain differences between first- and second generation antipsychotics with respect of regional selectivity for dopamine and serotonin neurons.