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The dopamine (DA) hypothesis of schizophrenia, which was based largely on evidence that pharmacological manipulations of DA systems influence the symptoms of schizophrenia, is undergoing a transformation due to our knowledge of the anatomy and pharmacology of additional subtypes of dopamine receptors. New research links the multiplicity of D2-like receptors to divergent neuroanatomic sites of suspected pathology in schizophrenia. We hypothesize that this research suggests that D2 receptors in the basal ganglia are the likely site of extrapyramidal symptoms and not antipsychotic effects. Rather, D3 receptors of the mesolimbic system are a likely site of antipsychotic effects, and D2 and D4 receptors in the medial temporal lobe and limbic cortical areas are the sites of additional antipsychotic effects. This work also suggests that divergent DA receptor circuits are likely associated with the pathophysiology of this disorder.

Linking the Family of D2 Receptors to Neuronal Circuits in Human Brain: Insights into Schizophrenia