The lonely mouse: a novel model to study the impact of prenatal depression and the effects of antidepressant treatment in the offspring

Antenatal psychopathology negatively affects obstetric outcomes and exerts long-term consequences on the offspring's wellbeing and mental health. However, the precise mechanisms underlying these associations remain largely unknown. We have developed a novel experimental model system in mice that allows for mechanistic investigation into the effects of antenatal maternal stress and for evaluating the influence of maternal pharmacological treatments on long-term outcomes in the offspring. This model system in based on rearing nulliparous female mice in social isolation prior to mating, leading to a depression-like state that is initiated before and continued throughout pregnancy. Using this model, we show that the maternal depression-like state induced by social isolation can be partially rescued by chronic treatment with the selective serotonin reuptake inhibitor, fluoxetine (FLX). Moreover, we identify a variety of behavioral and molecular abnormalities, including increased anxiety-like behavior, cognitive impairments and alterations of the amygdalar transcriptome, in male and female offspring born to socially isolated mothers relative to offspring born to mothers that were maintained in social groups prior to conception. We also found that maternal FLX treatment was effective in preventing some of the behavioral and molecular abnormalities emerging in offspring born to socially isolated mothers. Taken together, our findings suggest that the presence of a depression-like state during preconception and pregnancy has negative consequences on brain and behavioral functions in the offspring. At the same time, our study highlights that FLX treatment in mothers with a depression-like state can prevent abnormal behavioral development in the offspring.