Abstract
Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.
Highlights
Maternal interactions and maternal care during early life are essential for the development of appropriate social skills in adulthood in humans, primates and rodents [1,2,3,4,5,6]
Since early stress has been implicated in antisocial behaviors [16], we examined whether social exploration was altered by MSUS in F1, F2 and F3 mice
These results suggest a combination of social anxiety and impaired social memory in MSUS mice that is transmitted across generations
Summary
Maternal interactions and maternal care during early life are essential for the development of appropriate social skills in adulthood in humans, primates and rodents [1,2,3,4,5,6]. To study the impact of compromised early environment on social behaviors and its potential inheritance, we used a model of postnatal stress in the mouse. This model is based on unpredictable maternal separation combined with maternal stress (MSUS), a paradigm that perturbs maternal care provided to pups during the separation period, but not to their subsequent offspring [9]. The impact of the manipulation on social behaviors was further assessed on two following generations (F2 and F3) by breeding adult F1 males to wild-type C57Bl/6J females, F2 males to wild-type females
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