Involvement of vasopressin V1b receptor in anti-anxiety action of SSRI and SNRI in mice

Arginine vasopressin (AVP) is critical in the regulation of hypothalamic-pituitary-adrenal axis activity, a major component of the stress response. The vasopressin V1b receptor (V1bR) mediates the stimulatory effect of AVP on adrenocorticotropin release. Previous studies showed that AVP facilitates aggression while serotonin inhibits aggression by blocking the activity of the vasopressin system. To examine whether the interaction of the V1bR and serotonin in the central nervous system controls anxiety-related behavior, we investigated the effects of acute and chronic treatment with a selective serotonin reuptake inhibitor (SSRI) and with a serotonin noradrenalin reuptake inhibitor (SNRI) on V1bR knockout (KO) mice and on V1bR antagonist (SSR149415)-treated mice. The effects were evaluated in experiments using an elevated plus-maze (EPM) test and a hole-board (HB) test, well established tests for evaluating anxiety-like behavior. For both the V1bR KO mice and V1bR antagonist-treated mice, acute treatment with either SSRI or SNRI did not change the time spent on the EPM open arms or the number of head dips in the HB. Chronic treatment of V1bR KO mice with SSRI did not change the amount of time spent on the open arms, the number of head dips, or the number of rearings, while chronic treatment with SNRI significantly increased the time spent on the open arms and the number of head dips. These results suggest that the anti-anxiety action of 5-HT reuptake inhibitors might partly involve V1bR regulating the anxiety behaviors.