Shaping brain development: mouse communal nesting blunts adult neuroendocrine and behavioral response to social stress and modifies chronic antidepressant treatment outcome

Abstract

Early experiences shape brain function and behavior and, consequently, vulnerability to psychopathology at adulthood. Here we exploited the mouse communal nest (CN) paradigm in order to investigate the effect of the early social environment on the emergence of endophenotypes of depression and on antidepressant efficacy at adulthood. CN, which consists in a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions, thus representing an highly stimulating environment. Our results show that, when compared to mice reared in standard laboratory conditions (SN), adult CN mice exhibited greater sucrose preference on the first days of the test, displayed reduced anhedonia during social stress and had lower corticosterone levels after acute and prolonged social stress. Furthermore, in line with previous work, CN displayed longer immobility than SN mice in the forced swim test. Here we show that such behavioral response is differently affected by antidepressants according to early experiences. A 3-week fluoxetine treatment affected only SN mice, leading to an increase of immobility duration up to the levels showed by CN mice, while acute fluoxetine administration decreased immobility duration in both groups. These results show that being reared in a CN profoundly changes developmental trajectories, reducing the adult display of endophenotypes of depression and modifying response to antidepressants. The present findings suggest that early experiences represent one of those factors to be taken into account to identify the appropriate individual pharmacological strategy to treat depression in patients.