Cognitive and social behaviour deficits at adulthood in female rat offspring of Poly I:C treated rat dams, a developmental model for schizophrenia

Ben Grayson, Victoria Fasolino, Michelle Edye, Joanna Oladipo, Nagi Idris, Michael Harte, Joanna C Neill

Manchester Pharmacy School, University of Manchester, Manchester, M13 9PT, UK

Introduction

Methods

Results

.

Conclusions

Social interaction

Sniffing

Avoidance Object exploration

Following

Novel object recognition

Based on the innate preference for novelty

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PND 41

PND 67

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PND 39

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Cohort: 1

PND 100

Cohort: 1

3h post poly I:C injection

Cohort: 2

3h post poly I:C injection

• Significant increase in IL-6

• Decrease in bodyweight

• Significant increase in IL-6

• Significant reduction in

body weight, placenta

weight & pup length.

• PolyI:C produces a trend toward a reduction

social behaviours in adolescent (PND 39) female

offspring.

• Enhanced reduction in social behaviours

following treatment with PolyI:C in adult (PND

66) in female offspring.

• PolyI:C treatment has no effect on novel object

recognition in adolescent (PND 41) male and

female offspring.

• PolyI:C treatment impairs novel object

recognition in adult (PND 67) female offspring.

• PolyI:C treatment significantly increases trials to

criterion in the EDS phase of the ASST in adult

(PND 100) female offspring.

PD100

set shift

Females

only

Reasoning and problem solving

Rat analogue of the ID/ED test in

CANTAB. Rewarded paradigm – 7

discriminations

Attentional Set-shifting:

ASST

Poly I:C (10 mg/kg, i.p.) administered to

Pregnant rats on GD 15.

Social Interaction Test Cohort: 1

Novel Object Recognition Test Cohort: 1

• Maternal Immune activation (mIA) by the administration of the viral-mimetic polyriboinosinic-polyribocytidylic acid (polyI:C) is a key model for

neurodevelopmental disorders (NDDs) such as schizophrenia (Knuesel et al, 2014).

• We have established that the most robust systemic inflammatory response to polyI:C is produced by an acute dose of 10 mg/kg, i.p. in rats of the Wistar strain

Aim

To investigate the physiological and behavioural consequences of mIA in male and female offspring at specific developmental time points.

Attentional set-shifting Task (ASST) Cohort: 1

We have developed a robust model of mIA in Wistar rats and used this to identify the longitudinal development of behavioural changes.

• PolyI:C (10 mg/kg,i.p.) at GD15 induced a variable but reproducible immune response (IL-6) in Wistar rats (cohort 1 & 2).

• At GD21 there were significant reductions in both male and female pup body weight, pup length and placenta weight (cohort 2). Placental weight reduction is a consistent finding.

• Significant behavioural deficits were not detectable during adolescence.

• Social behaviour deficits seemed to be emerging and a cognitive phenotype was clearly observed in adult females, particularly in the prefrontal cortical mediated ASST at the later

stage of PND 100.

Neurobiological mechanisms for the behavioural effects are currently being investigated.

Cohort: 2

GD21