Maternal immune activation alters sensitivity to action-outcome contingency in adult rat offspring.

Abstract

Epidemiological studies have provided convincing evidence for a role of maternal immune activation in the pathogenesis of neurodevelopmental disorders such as autism and schizophrenia. In recent years, several research groups have capitalised on this discovery and developed animal models such as the maternal immune activation (MIA) model that emulates many phenotypes characteristic of disorders such as schizophrenia. In the present series of experiments we used the MIA model to examine motivation, a core component of the negative symptomatology in schizophrenia. Contrary to what we expected, in the progressive ratio task, which assesses an animals' willingness to work for a reward under increasing effort requirements, we found that MIA rats appeared more motivated than controls. Subsequent tests showed that this seemingly enhanced motivation was not due to an overall increase in responding, nor due to enhanced attribution of incentive salience to reward associated responses. Instead, we found that the increased willingness to work exhibited by MIA animals was due to an inability to detect changes in the contingency between their behaviour and the resulting rewarding outcome. With regard to motivation, the experiments reported here are the first to subject the MIA model to a rigorous experimental analysis of behaviour by parsing underlying processes that give rise to the overt symptoms in psychiatric disease.