Objective: Measurement of behavioral responses to antipsychotic (clozapine, chlorpromazine) and psychomimetic (ketamine) drug administration in offspring of pregnant mice exposed to influenza virus
Materials & Equipment Checklist
9 items1 from ConductScience
Gather these items before starting the experiment. Check off items as you prepare.
Equipment3
not specified • not specified • not specified • not specified
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View Abstract
Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
Protocol Steps
1
Maternal viral infection
Pregnant mice (BALB/c and C57BL/6 strains) are exposed to respiratory infection with human influenza virus
not specifiednot specified
Note: Infection occurs during pregnancy to produce offspring with behavioral abnormalities
View evidence from paper
“respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults”
2
Prepulse inhibition (PPI) testing
Adult offspring are tested for deficits in prepulse inhibition in the acoustic startle response
Note: Comparison made between infected and control mice
View evidence from paper
“these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response”
3
Drug response assessment - antipsychotics
Acute administration of antipsychotic drugs (clozapine and chlorpromazine) to assess behavioral responses in infected versus control mice
not specifiednot specified
Note: Infected mice display striking responses compared to control mice
View evidence from paper
“Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine)”
4
Drug response assessment - psychomimetic
Acute administration of psychomimetic drug (ketamine) to assess behavioral responses in infected versus control mice
not specifiednot specified
Note: Infected mice display striking responses compared to control mice
View evidence from paper
“striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs”
5
Open-field testing
Adult offspring are tested for exploratory behavior deficits in open-field apparatus
not specifiednot specified
Note: Infected mice show deficient exploratory behavior compared to controls
View evidence from paper
“mice are deficient in exploratory behavior in both open-field and novel-object tests”
6
Novel-object testing
Adult offspring are tested for exploratory behavior deficits with novel objects
not specifiednot specified
Note: Infected mice show deficient exploratory behavior compared to controls
View evidence from paper
“mice are deficient in exploratory behavior in both open-field and novel-object tests”
7
Social interaction testing
Adult offspring are assessed for deficits in social interaction
not specifiednot specified
Note: Infected mice show deficient social interaction compared to controls
View evidence from paper
“they are deficient in social interaction”
8
Maternal immune response control experiment
Pregnant mice receive maternal injection of synthetic double-stranded RNA (poly(I:C)) without viral infection to assess immune response effects
not specifiednot specified
Note: Poly(I:C) injection alone causes PPI deficit in offspring, suggesting maternal immune response is responsible for behavioral changes
View evidence from paper
“maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus”
Subjects / Specimens
Species
mouse
Strain
BALB/c and C57BL/6
Age
adult
Sex
not specified
Count
not specified
Weight
not specified
Offspring of pregnant mice infected with human influenza virus during pregnancy