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Endogenous kynurenic acid disrupts prepulse inhibition
Sophie Erhardt1, Lilly Schwieler, Carolina Emanuelsson
1Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. Sophie.Erhardt@fyfa.ki.se
Biological Psychiatry
|August 18, 2004
Summary
Elevated kynurenic acid (KYNA) in the brain significantly impairs sensorimotor gating, measured by prepulse inhibition (PPI). Antipsychotic drugs reversed this effect, suggesting KYNA
Area of Science:
- Neuroscience
- Psychopharmacology
Background:
- Elevated kynurenic acid (KYNA) levels are observed in schizophrenia patients.
- Prepulse inhibition (PPI) assesses sensorimotor gating, which is impaired in schizophrenia.
- NMDA receptor antagonists cause deficits in sensorimotor gating.
Purpose of the Study:
- To investigate the effects of endogenous KYNA on startle and PPI in rats.
- To explore KYNA's role as an endogenous N-methyl-D-aspartate (NMDA) receptor antagonist.
Main Methods:
- Increased endogenous brain KYNA levels via kynurenine or PNU 156561A administration in rats.
- Measured startle reflex and PPI.
- Administered haloperidol or clozapine to assess PPI restoration.
Main Results:
- Increased brain KYNA significantly reduced PPI.
- No changes in startle magnitudes were observed.
- Haloperidol and clozapine restored the disrupted PPI.
Conclusions:
- Brain KYNA acts as an endogenous modulator of PPI.
- Findings support the hypothesis that KYNA contributes to schizophrenia pathophysiology.