4.7 Article

Effects of immune activation during early or late gestation on schizophrenia-related behaviour in adult rat offspring

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 63, Issue -, Pages 8-20

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2016.07.144

Keywords

Maternal immune activation; Poly (I:C); Gestational timing; Rat; Schizophrenia; Working memory; Dopamine; Sensorimotor gating; Neurodevelopment

Funding

  1. National Health and Medical Research Council (NHMRC) of Australia [APP1026070]
  2. Hunter Medical Research Institute
  3. Australian Postgraduate Award
  4. NHMRC [APP1026070, APP1109283]
  5. Schizophrenia Research Institute, New South Wales Health, Australia
  6. New South Wales Department of Trade Investment
  7. Schizophrenia Research Institute (NSW Ministry of Health)
  8. Schizophrenia Research Institute (Macquarie Group Foundation)
  9. University of New South Wales
  10. Neuroscience Research Australia
  11. NHMRC (Australia) Senior Research Fellowship [1021970]

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Maternal exposure to infectious agents during gestation has been identified as a significant risk factor for schizophrenia. Using a mouse model, past work has demonstrated that the gestational timing of the immune-activating event can impact the behavioural phenotype and expression of dopaminergic and glutamatergic neurotransmission markers in the offspring. In order to determine the inter-species generality of this effect to rats, another commonly used model species, the current study investigated the impact of a viral mimetic Poly (I:C) at either an early (gestational day 10) or late (gestational day 19) time-point on schizophrenia-related behaviour and neurotransmitter receptor expression in rat offspring. Exposure to Poly (I:C) in late, but not early, gestation resulted in transient impairments in working memory. In addition, male rats exposed to maternal immune activation (MIA) in either early or late gestation exhibited sensorimotor gating deficits. Conversely, neither early nor late MIA exposure altered locomotor responses to MK-801 or amphetamine. In addition, increased dopamine 1 receptor mRNA levels were found in the nucleus accumbens of male rats exposed to early gestational MIA. The findings from this study diverge somewhat from previous findings in mice with MIA exposure, which were often found to exhibit a more comprehensive spectrum of schizophrenia-like phenotypes in both males and females, indicating potential differences in the neurodevelopmental vulnerability to MIA exposure in the rat with regards to schizophrenia related changes. (C) 2016 Published by Elsevier Inc.

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