Effects of early life stress on adult male aggression and hypothalamic vasopressin and serotonin

Early life stress in humans enhances the risk for psychopathologies, including excessive aggression and violence. In rodents, maternal separation is a potent early life stressor inducing long-lasting changes in emotional and neuroendocrine responsiveness to stress, associated with depression- and anxiety-like symptoms. However, effects of maternal separation on adult male aggression and underlying neurobiological mechanisms remain unknown. Therefore, we investigated the effects of maternal separation on adult intermale aggression in Wistar rats and on hypothalamic arginine vasopressin (AVP) mRNA expression, and AVP and serotonin (5-HT) immunoreactivity, as both AVP and 5-HT have been implicated in stress-coping and aggression. We showed that maternal separation induced depression-like behaviour (increased immobility) and higher adrenocorticotropin hormone responses to an acute stressor (forced swimming). Intermale aggression (lateral threat, offensive upright and keep down) was significantly higher in maternally separated rats compared with control rats. AVP mRNA expression and AVP immunoreactivity were higher in the hypothalamic paraventricular and supraoptic nuclei upon resident-intruder test exposure, whereas 5-HT immunoreactivity was decreased in the anterior hypothalamus of maternally separated rats. Moreover, 5-HT immunoreactivity in the anterior hypothalamus and supraoptic nucleus correlated negatively with aggression. These findings show that exposure to early life stress increases adult male aggression in an animal model of maternal separation. Furthermore, the maternal separation-induced changes in hypothalamic AVP and 5-HT systems may underlie these behavioural alterations.