Increased N-acetylaspartate in rat striatum following long-term administration of haloperidol

Schizophr Res. 2005 Jun 15;75(2-3):303-8. doi: 10.1016/j.schres.2004.11.001. Epub 2004 Dec 1.


N-acetylaspartate (NAA) is present in high concentrations in the CNS and is found primarily in neurons. NAA is considered to be a marker of neuronal viability. Numerous magnetic resonance spectroscopy (MRS) and postmortem studies have shown reductions of NAA in different brain regions in schizophrenia. Most of these studies involved patients chronically treated with antipsychotic drugs. However, the effect of chronic antipsychotic treatment on NAA remains unclear. In the present study, we measured NAA in brain tissue taken from 43 male Long-Evans rats receiving 28.5 mg/kg haloperidol decanoate i.m. every 3 weeks for 24 weeks and from 21 controls administered with vehicle. Determination of tissue concentrations of NAA was achieved by HPLC of sections of frozen tissue from several brain regions with relevance to schizophrenia. Chronic administration of haloperidol was associated with a significant increase (+23%) in NAA in the striatum (p<0.05) when compared to controls, with no significant changes in the other regions investigated (frontal and temporal cortex, thalamus, hippocampus, amygdala, and nucleus accumbens). NAA appears to be selectively increased in the striatum of rats chronically receiving haloperidol. This increase may reflect a hyperfunction of striatal neurons and relate to the reported increase in somal size of these cells and/or the increase in synaptic density seen in this region following antipsychotic administration. The lack of effect in other regions indicates that the well-documented NAA deficits seen in chronically treated schizophrenia patients is not an effect of antipsychotic medication and may in fact be related to the disease process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Dose-Response Relationship, Drug
  • Haloperidol / administration & dosage
  • Haloperidol / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Male
  • Rats
  • Rats, Long-Evans
  • Time Factors


  • Antipsychotic Agents
  • Aspartic Acid
  • N-acetylaspartate
  • Haloperidol