Cognitive, Behavioral, and Systems NeuroscienceResearch PaperAltered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy
Highlights
▶Behavioral effects of prenatal PolyI:C treatment were examined in both male and female prepubescent and adult Long Evans rats. ▶Disrupted prepulse inhibition and locomotor activity were observed in male and female offspring exposed to PolyI:C. ▶Neither object nor object location recognition memory was altered by prenatal exposure to PolyI:C. ▶Prefrontal-dependent object-in-place memory was severely disrupted in adult male offspring exposed to PolyI:C.
Section snippets
Subjects
Timed pregnant Long–Evans dams (GD 7; Charles River Laboratories, Quebec, Canada) were singly housed in transparent plastic cages in a temperature-controlled (21 °C) colony room on a 12/12-h light/dark cycle with food (Purina Rat Chow) and water available ad libitum. The offspring of four separate squads of dams purchased between January 2010 and January 2011 were used in the present experiments. Some animals were siblings of those reported in Zhang et al. (in press). Maternal observations were
Effects of PolyI:C treatment on dams and pups
Weight and rectal temperature of all dams were taken 0, 8, 24, and 48 h following PolyI:C injection. Human error resulted in the loss of weight data for one dam and temperature data for five dams. Statistical analysis of dam weights revealed significant main effects of Time (F(3,87)=45.72, P<0.001), Treatment (F(1,29)=5.11, P=0.031), and a significant Treatment by Time interaction (F(3,87)=17.28, P<0.001). Inspection of the data revealed that dam weights were significantly lower for the saline
Discussion
The present study examined the influence of prenatal immune challenge with PolyI:C on PPI of the acoustic startle response, locomotor activity, and recognition memory in Long Evans rats. Consistent with previous reports, PolyI:C treatment caused significant weight loss in the dams and a subtle increase in temperature (Fig. 1). With prepulse-pulse intervals of 50, 80, and 140 ms, PolyI:C treatment disrupted PPI before puberty and in young adulthood (Fig. 2). Enhanced prepulse facilitation was
Conclusion
The present experiments demonstrate that prenatal immune challenge results in cognitive and behavioral disruptions in rats similar to those reported in patients with neurodevelopmental psychiatric disorders such as schizophrenia. The specificity of the recognition memory deficit to the object-in-place test suggests that cognitive functions associated with the prefrontal cortex may be particularly susceptible to alteration following prenatal infection. The relative ease of conducting these tasks
Acknowledgments
The present work was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression, Saskatchewan Health Research Foundation New Investigator Award, and University of Saskatchewan Molstad Trust Intramural Research Award to J.G.H. B.N.C. is the recipient of a National Sciences and Engineering Research Council of Canada Graduate Scholarship. We would like to thank Chester Thai and Quentin Greba for technical assistance with these experiments.
References (82)
- et al.
Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus
Biol Psychiatry
(2001) - et al.
Cognitive functions in prepsychotic patients
Prog Neuropsychopharmacol Biol Psychiatry
(2005) - et al.
Individual differences in maternal response to immune challenge predict offspring behavior: contribution of environmental factors
Behav Brain Res
(2011) - et al.
Pharmacological and parametrical investigation of prepulse inhibition of startle and prepulse elicited reactions in Wistar rats
Pharmacol Biochem Behav
(2011) - et al.
Impaired performance in a working memory binding task in patients with schizophrenia
Psychiatry Res
(2004) - et al.
Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat
Behav Brain Res
(2000) - et al.
NMDA receptor function, neuroplasticity, and the pathophysiology of schizophrenia
Int Rev Neurobiol
(2004) - et al.
Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy
Behav Brain Res
(2009) - et al.
Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition
Behav Brain Res
(1999) - et al.
Prepulse inhibition of startle in adults with ADHD
J Psychiatr Res
(2009)
Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy
Behav Brain Res
Neurosteroids affect spatial/reference, working, and long-term memory of female rats
Neurobiol Learn Mem
Statistical issues and techniques appropriate for developmental neurotoxicity testing: a report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints
Neurotoxicol Teratol
Effects of acute stress and GluN2B-containing NMDA receptor antagonism on object and object-place recognition memory
Neurobiol Learn Mem
Kindling of basolateral amygdala but not ventral hippocampus or perirhinal cortex disrupts sensorimotor gating in rats
Behav Brain Res
Electrical stimulation of the hippocampus disrupts prepulse inhibition in rats: frequency- and site-dependent effects
Behav Brain Res
Activation of the maternal immune system induces endocrine changes in the placenta via IL-6
Brain Behav Immun
Effects of background and prepulse characteristics on prepulse inhibition and facilitation: implications for neuropsychiatric research
Biol Psychiatry
Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood
Neurosci Res
Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring
Brain Behav Immun
The neurobiology of startle
Prog Neurobiol
Neural basis of psychosis-related behaviour in the infection model of schizophrenia
Behav Brain Res
Epidemiology-driven neurodevelopmental animal models of schizophrenia
Prog Neurobiol
In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders
Neurosci Biobehav Rev
Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia
Neurosci Biobehav Rev
Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice
Brain Behav Immun
Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia
Biol Psychiatry
Immune involvement in schizophrenia and autism: etiology, pathology and animal models
Behav Brain Res
Sensorimotor gating deficits in adults with autism
Biol Psychiatry
Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia
Biol Psychiatry
Acoustic prepulses can facilitate the startle reflex in rats: discrepancy between rat and human data resolved
Brain Res Bull
Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation
J Psychiatr Res
Effect of paliperidone and risperidone on extracellular glutamate in the prefrontal cortex of rats exposed to prenatal immune activation or MK-801
Neurosci Lett
Influence of gender on working and spatial memory in the novel object recognition task in the rat
Behav Brain Res
Immune activation during mid-gestation disrupts sensorimotor gating in rat offspring
Behav Brain Res
The maternal immune activation (MIA) model of schizophrenia produces pre-pulse inhibition (PPI) deficits in both juvenile and adult rats but these effects are not associated with maternal weight loss
Behav Brain Res
Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings
Biol Psychiatry
Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia
Pharmacol Ther
Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring
J Psychiatr Res
Daily functioning and information-processing skills among persons with schizophrenia
Psychiatr Serv
Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex
J Neurosci
Cited by (104)
Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats
2023, Neurobiology of StressThe long-lasting effects of early antipsychotic exposure during juvenile period on adult behaviours – A study in a poly I:C rat model
2022, Pharmacology Biochemistry and BehaviorReelin has antidepressant-like effects after repeated or singular peripheral injections
2022, NeuropharmacologyMaternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic
2021, Brain, Behavior, and Immunity - Health