Effects of prenatal immune activation on amphetamine-induced addictive behaviors: Contributions from animal models

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Prenatal environmental adversities may affect brain development and are associated with increased risk for schizophrenia, an illness with 50% comorbidity with addiction. Maternal immune activation by poly-inosinic–citidilic acid (Poly(I:C)) exposure can promote behavioral alterations consistent with schizophrenia symptoms in rodents.


Considering the vulnerability to addiction in patients with schizophrenia, we evaluated the interactions between prenatal Poly(I:C) administration and addiction in two animal models (behavioral sensitization and conditioned place preference — CPP) in mice repeatedly treated with amphetamine (AMP). Additionally, stereotyped behavior and cross-sensitization with cocaine (COC) were also investigated.


Swiss male mice offspring were submitted to prenatal administration of 5 mg/kg Poly(I:C) in the 9th day of pregnancy. At the age of 90 days, mice were treated with 2.5 mg/kg AMP for 9 days to evaluate behavioral sensitization or stereotyped behavior. Cross-sensitization with 10 mg/kg COC was evaluated 24 h after the last treatment day. For AMP-induced CPP evaluation, mice were treated during 8 consecutive days.


Prenatal Poly(I:C) administration potentiated both AMP-induced behavioral sensitization and CPP. Furthermore, Poly(I:C) increased cross-sensitization with COC.


Prenatal administration of Poly(I:C) is able to potentiate vulnerability to addiction in two animal models, without however modulating stereotyped behavior.

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