Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions.

The D(3) receptor may represent an important target for antipsychotic drugs which all bind with high affinity and do not induce upon repeated administration either tolerance or receptor upregulation. The D(3) receptor is localized in brain areas, namely the nucleus accumbens and cerebral cortex, implicated in neural circuits believed to display defective functioning in schizophrenia. Overexpression of the D(3) receptor, which accounts for the behavioral sensitization to levodopa in a rodent model of Parkinson's disease, might also be responsible for the sensitization to dopamine agonists observed in schizophrenia. The appearance of the D(3) receptor during brain development, early in proliferating neuroepithelia and later in neurons from limbic areas, suggests further studies to assess its participation in the neurodevelopmental disorders of schizophrenia. Finally, meta-analysis of approximately 30 studies comprising over 2500 patients indicate that a polymorphism in the coding sequence of the D(3) receptor is associated with a small but significant enhancement of vulnerability to the disease.