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Brain Behav Immun. 2014 Feb;36:80-9. doi: 10.1016/j.bbi.2013.10.010. Epub 2013 Oct 17.

Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment--role of brain kynurenic acid.

Author information

1
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
2
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
3
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
4
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address: sophie.erhardt@ki.se.

Abstract

Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subsequent behavioral disturbances in immune-deficient adult mice. The aim of the present study was to investigate a potential role in this regard of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N-methyl-D-aspartic acid (NMDA) receptor and at the cholinergic α7 nicotinic receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33 virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine (2×200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse inhibition of the acoustic startle, anxiety, and learning and memory were also assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L-kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as well as mild impairments in prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine release in the striatum in kynurenine-treated mice. These long-lasting behavioral and neurochemical alterations suggest that the kynurenine pathway can link early-life infection with the development of neuropsychiatric disturbances in adulthood.

KEYWORDS:

Amphetamine; Immune activation; Kynurenine; Locomotor activity; Microdialysis; Neurodevelopment; Postnatal; Prepulse inhibition; Schizophrenia

PMID:
24140727
PMCID:
PMC3947209
DOI:
10.1016/j.bbi.2013.10.010
[Indexed for MEDLINE]
Free PMC Article

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