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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liu, X-C; Holtze, M; Powell, SB; Terrando, N; Larsson, MK; Persson, A; Olsson, SK; Orhan, F; Kegel, M; Asp, L; Goiny, M; Schwieler, L; Engberg, G; Karlsson, H; Erhardt, S

Published Date

  • February 2014

Published In

Volume / Issue

  • 36 /

Start / End Page

  • 80 - 89

PubMed ID

  • 24140727

Electronic International Standard Serial Number (EISSN)

  • 1090-2139

International Standard Serial Number (ISSN)

  • 0889-1591

Digital Object Identifier (DOI)

  • 10.1016/j.bbi.2013.10.010

Language

  • eng