Possible implications of the dopamine D-3 receptor in schizophrenia and inantipsychotic 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 administr ation either tolerance or receptor upregulation. The Dg receptor is localiz ed in brain areas, namely the nucleus accumbens and cerebral cortex, implic ated in neural circuits believed to display defective functioning in schizo phrenia. Overexpression of the D-3 receptor, which accounts for the behavio ral sensitization to levodopa in a rodent model of Parkinson's disease, mig ht also be responsible for the sensitization to dopamine agonists observed in schizophrenia. The appearance of the D-3 receptor during brain developme nt, early in proliferating neuroepithelia and later in neurons from limbic areas, suggests further studies to assess its participation in the neurodev elopmental disorders of schizophrenia. Finally, meta-analysis of similar to 30 studies comprising over 2500 patients indicate that a polymorphism in t he coding sequence of the D-3 receptor is associated with a small but signi ficant enhancement of vulnerability to the disease. (C) 2000 Elsevier Scien ce B.V. All rights reserved.