Abnormal context-reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia
Open access
Date
2015-09Type
- Journal Article
Abstract
Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite itsclinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used anepidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-relatedfunctions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to theepidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternalinfection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditionedplace preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the otherhand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated thelocomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextualfear conditioning paradigm. Ourfindings suggest that the nature of reward-related abnormalities following prenatal immunechallenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vsnegative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context–reward associations andto integrate such information for appropriate goal-directed behavior. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000105185Publication status
publishedExternal links
Journal / series
Translational PsychiatryVolume
Pages / Article No.
Publisher
NatureOrganisational unit
03274 - Langhans, Wolfgang (emeritus)
Funding
146217 - Inflammation-mediated epigenetic priming of neurodevelopmental disease (SNF)
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