Adolescent stress and neural plasticity in hamsters: a vasopressin-serotonin model of inappropriate aggressive behaviour.

Animal studies show that arginine vasopressin facilitates aggression, while serotonin (5-HT) inhibits aggression by blocking the activity of the vasopressin system. Clinical studies report that subjects with a history of 'fighting and assault' show a significant positive correlation between cerebrospinal fluid concentrations of vasopressin and aggression in the presence of a hyporeactive 5-HT system. Thus, in animals and humans, a hyporeactive 5-HT system may result in enhanced vasopressin activity and increased aggression. Can the stress of emotional and physical insult, i.e. threat and attack, during adolescence affect the development of the vasopressin and 5-HT systems and alter normal aggressive behaviour in early adulthood? Adolescent male golden hamsters were weaned at postnatal day 25, and stressed for 2 weeks by daily 1 h bouts of threat and attack by adult hamsters. Male littermates were run in a parallel stress study using daily 1 h trials of isolation in a novel environment. During early adulthood, on postnatal day 45, 3 days after the cessation of stress trials, animals were tested for aggression in a resident: intruder model. The results show a context-dependent change in aggression. Animals with a history of abuse show exaggerated attack behaviour toward smaller males compared to littermates with a history of isolation stress. Conversely, when confronted by males of equal size, animals with a history of abuse show diminished aggression and increased submission compared to controls. It was determined that the density of vasopressin fibres and neurones in the hypothalamus is lower in abused animals compared to controls. In contrast, the number of 5-HT terminals within the hypothalamus is higher in abused animals compared to controls. These results provide evidence in an animal model that stress in the form of threat and attack during adolescence can alter the balance between vasopressin and 5-HT in the brain, resulting in inappropriate aggressive behaviour in early adulthood.