Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression.C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS

Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2

The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA (N-methyl-D-aspartic acid) receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator