Metabolic Brain Disease

, Volume 26, Issue 3, pp 237–240 | Cite as

Peripheral immune challenge with viral mimic during early postnatal period robustly enhances anxiety-like behavior in young adult rats

  • Gregory W. Konat
  • Brent E. Lally
  • Anastasia A. Toth
  • Adrienne K. Salm
Short Communication


Inflammatory factors associated with immune challenge during early brain development are now firmly implicated in the etiologies of schizophrenia, autism and mood disorders later in life. In rodent models, maternal injections of inflammagens have been used to induce behavioral, anatomical and biochemical changes in offspring that are congruent with those found in human diseases. Here, we studied whether inflammatory challenge during the early postnatal period can also elicit behavioral alterations in adults. At postnatal day 14, rats were intraperitoneally injected with a viral mimic, polyinosinic:polycytidylic acid (PIC). Two months later, these rats displayed remarkably robust and consistent anxiety-like behaviors as evaluated by the open field/defensive-withdrawal test. These results demonstrate that the window of vulnerability to inflammatory challenge in rodents extends into the postnatal period and offers a means to study the early sequelae of events surrounding immune challenge to the developing brain.


Immune-to-brain communication Polyinosinic:polycytidylic acid Acute antiviral response Inflammation Anxiety disorders Schizophrenia 


  1. Blanchard RJ, Kelley MJ, Blanchard DC (1974) Defensive reactions and exploratory behavior in rats. J Comp Physiol Psychol 87:1129–1133CrossRefGoogle Scholar
  2. Dickerson PA, Lally BE, Gunnel E, Birkle DL, Salm AK (2005) Early emergence of increased fearful behavior in prenatally stressed rats. Physiol Behav 86:586–593PubMedCrossRefGoogle Scholar
  3. Galic MA, Riazi K, Heida JG, Mouihate A, Fournier NM, Spencer SJ, Kalynchuk LE, Teskey GC, Pittman QJ (2008) Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci 28:6904–6913PubMedCrossRefGoogle Scholar
  4. Guha-Thakurta N, Majde JA (1997) Early induction of proinflammatory cytokine and type I interferon mRNAs following Newcastle disease virus, poly [rI:rC], or low-dose LPS challenge of the mouse. J Interferon Cytokine Res 17:197–204PubMedCrossRefGoogle Scholar
  5. Hsu FC, Zhang GJ, Raol YS, Valentino RJ, Coulter DA, Brooks-Kayal AR (2003) Repeated neonatal handling with maternal separation permanently alters hippocampal GABAA receptors and behavioral stress responses. Proc Natl Acad Sci USA 100:12213–12218PubMedCrossRefGoogle Scholar
  6. Ibi D, Nagai T, Kitahara Y, Mizoguchi H, Koike H, Shiraki A, Takuma K, Kamei H, Noda Y, Nitta A, Nabeshima T, Yoneda Y, Yamada K (2009) Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood. Neurosci Res 64:297–305PubMedCrossRefGoogle Scholar
  7. Ibi D, Nagai T, Koike H, Kitahara Y, Mizoguchi H, Niwa M, Jaaro-Peled H, Nitta A, Yoneda Y, Nabeshima T, Sawa A, Yamada K (2010) Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. Behav Brain Res 206:32–37PubMedCrossRefGoogle Scholar
  8. Konat G, Clausen J (1976) Triethyl lead-induced hypomyelination in the developing rat forebrain. Exp Neuro 150:124–133CrossRefGoogle Scholar
  9. Kuhn HG, Blomgren K (2011) Developmental dysregulation of adult neurogenesis. Eur J Neurosci 33:1115–1122CrossRefGoogle Scholar
  10. Li Q, Cheung C, Wei R, Cheung V, Hui ES, You Y, Wong P, Chua SE, McAlonan GM, Wu EX (2010) Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy. Neuroimage 52:1–8PubMedCrossRefGoogle Scholar
  11. Meyer U, Feldon J (2009) Neural basis of psychosis-related behaviour in the infection model of schizophrenia. Behav Brain Res 204:322–334PubMedCrossRefGoogle Scholar
  12. Meyer U, Feldon J, Yee BK (2009) A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull 35:959–972PubMedCrossRefGoogle Scholar
  13. Meyer U, Feldon J (2010) Epidemiology-driven neurodevelopmental animal models of schizophrenia. Prog Neurobiol 90:285–326PubMedCrossRefGoogle Scholar
  14. Meyer U, Feldon J (2011) To poly(I:C) or not to poly(I:C): advancing preclinical schizophrenia research through the use of prenatal immune activation models. Neuropharmacology (Epub ahead of print)Google Scholar
  15. Rowland LM, Spieker EA, Francis A, Barker PB, Carpenter WT, Buchanan RW (2009) White matter alterations in deficit schizophrenia. Neuropsychopharmacology 34:1514–1522PubMedCrossRefGoogle Scholar
  16. Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophr Res 49:1–52PubMedCrossRefGoogle Scholar
  17. Spencer SJ, Martin S, Mouihate A, Pittman QJ (2006) Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge. Neuropsychopharmacology 31:1910–1918PubMedCrossRefGoogle Scholar
  18. Traynor TR, Majde JA, Bohnet SG, Krueger JM (2004) Intratracheal double-stranded RNA plus interferon-gamma: a model for analysis of the acute phase response to respiratory viral infections. Life Sci 74:2563–2576PubMedCrossRefGoogle Scholar
  19. Ward HE, Johnson EA, Salm AK, Birkle DL (2000) Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav 70:359–366PubMedCrossRefGoogle Scholar
  20. Weinstock M (2008) The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 32:1073–86PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gregory W. Konat
    • 1
  • Brent E. Lally
    • 1
  • Anastasia A. Toth
    • 1
  • Adrienne K. Salm
    • 1
  1. 1.Department of Neurobiology and AnatomyWest Virginia University School of MedicineMorgantownUSA

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