Role of D3 dopamine receptors in modulating neuroanatomical changes in response to antipsychotic administration

Sci Rep. 2019 May 24;9(1):7850. doi: 10.1038/s41598-019-43955-4.


Clinical research has shown that chronic antipsychotic drug (APD) treatment further decreases cortical gray matter and hippocampus volume, and increases striatal and ventricular volume in patients with schizophrenia. D2-like receptor blockade is necessary for clinical efficacy of the drugs, and may be responsible for inducing these volume changes. However, the role of other D2-like receptors, such as D3, remains unclear. Following our previous work, we undertook a longitudinal study to examine the effects of chronic (9-week) typical (haloperidol (HAL)) and atypical (clozapine (CLZ)) APDs on the neuroanatomy of wild-type (WT) and dopamine D3-knockout (D3KO) mice using magnetic resonance imaging (MRI) and histological assessments in a sub-region of the anterior cingulate cortex (the prelimbic [PL] area) and striatum. D3KO mice had larger striatal volume prior to APD administration, coupled with increased glial and neuronal cell density. Chronic HAL administration increased striatal volume in both WT and D3KO mice, and reduced PL area volume in D3KO mice both at trend level. CLZ increased volume of the PL area of WT mice at trend level, but decreased D3KO PL area glial cell density. Both typical and atypical APD administration induced neuroanatomical remodeling of regions rich in D3 receptor expression, and typically altered in schizophrenia. Our findings provide novel insights on the role of D3 receptors in structural changes observed following APD administration in clinical populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Cell Count
  • Clozapine / pharmacology
  • Clozapine / therapeutic use
  • Corpus Striatum / anatomy & histology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Female
  • Gyrus Cinguli / anatomy & histology
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / drug effects*
  • Haloperidol / pharmacology
  • Haloperidol / therapeutic use
  • Humans
  • Injections, Intraperitoneal
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neuroglia / drug effects
  • Neurons / drug effects
  • Organ Size / drug effects
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / pathology
  • Receptors, Dopamine D3 / genetics
  • Receptors, Dopamine D3 / metabolism*
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology


  • Antipsychotic Agents
  • Drd3 protein, mouse
  • Receptors, Dopamine D3
  • Clozapine
  • Haloperidol