Expressing emotions: Avp and Crh are involved in the phenotype of mice bred for extremes in anxiety-related behavior

To investigate the pathology of anxiety, mice were selected for extremes in anxiety-related behavior and gave rise to high (HAB) or low anxiety-related behavior (LAB) mice. An unbiased microarray approach confirmed, among other genes, the formerly described two-fold overexpression of vasopressin (Avp) and corticotropin-releasing hormone (Crh) in HAB compared to LAB mice. LAB animals also display an AVP-deficit on peptide level compared to HAB and CD1 mice. Additionally, a significant, positive correlation between immobility time in the tail suspension test and Avp mRNA could be shown, including data from all three lines. Furthermore, icv administration of a V1a/b receptor antagonist caused a decrease in immobility time in HAB mice, thus highlighting the functional involvement of AVP in depression-like behavior. In contrast, Crh is significantly higher expressed in HAB mice in comparison to the two other lines, a phenomenon validated via i.p. administration of a CRHR1 (DMP696) antagonist, causing an anxiolytic effect exclusively in HAB animals. Taken together, AVP is causally involved in mediating depression-like behavior, whereas CRH mainly contributes to the anxious HAB phenotype as shown by its overexpression and the anxiolytic effect of the receptor antagonist treatment. The differences in expression profiles together with the results of the antagonist studies confirm a critical involvement of both AVP and CRH in mediating anxiety-related and depression-like behavior.