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Journal of Neural Transmission

, Volume 113, Issue 10, pp 1355–1365 | Cite as

Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat brain

  • G. Ceresoli-Borroni
  • A. Rassoulpour
  • H.-Q. Wu
  • P. Guidetti
  • R. Schwarcz
Article

Summary.

The brain and cerebrospinal fluid levels of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist of the glycineB receptor and the α7 nicotinic acetylcholine receptor, are elevated in persons with schizophrenia. To evaluate whether this increase is related to antipsychotic medication, we examined the effects of haloperidol (HAL), clozapine (CLOZ) or raclopride (RAC) on brain KYNA levels in rats. Animals received either acute drug injections or ingested the drugs chronically with the drinking water. Acute application or one-week drug exposure had no effect on brain KYNA levels. After one month, HAL, CLOZ and RAC all caused significant reductions in KYNA levels in striatum, hippocampus and frontal cortex. Quantitatively similar reductions in the brain tissue content of KYNA were observed after one year of HAL administration. All these effects were accompanied by equivalent decreases in the extracellular concentration of KYNA, measured by striatal microdialysis. Separate animals received an intrastriatal infusion of 3H-kynurenine to probe the entire kynurenine pathway acutely in rats treated with HAL for one year. These animals showed reduced 3H-KYNA production, but no changes in the formation of other kynurenine pathway metabolites. By enhancing glutamatergic and cholinergic neurotransmission, reduced brain KYNA levels may play a role in the clinical effects of prolonged antipsychotic medication.

Keywords: Antipsychotics, clozapine, haloperidol, kynurenine pathway, raclopride, schizophrenia. 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • G. Ceresoli-Borroni
    • 1
  • A. Rassoulpour
    • 1
  • H.-Q. Wu
    • 1
  • P. Guidetti
    • 1
  • R. Schwarcz
    • 1
  1. 1.Maryland Psychiatric Research Center, University of Maryland School of MedicineBaltimoreUSA

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