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

Background: 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 polyinosinic-citidilic acid (Poly(I:C)) exposure can promote behavioral alterations consistent with schizophrenia symptoms in rodents. Objectives: 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. Methods: 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. Results: Prenatal Poly(I:C) administration potentiated both AMP-induced behavioral sensitization and CPP. Furthermore, Poly(I:C) increased cross-sensitization with COC. Conclusions: Prenatal administration of Poly(I:C) is able to potentiate vulnerability to addiction in two animal models, without however modulating stereotyped behavior. (C) 2015 Elsevier Inc. All rights reserved.