Social avoidance and altered hypothalamic-pituitary-adrenal axis in a mouse model of anxious depression: The role of LPA1 receptor

Anxious depression is a prevalent disease with devastating consequences. Despite the lack of knowledge about the neurobiological basis of this subtype of depression, recently our group has identified a relationship between the LPA₁ receptor, one of the six characterized G protein-coupled receptors (LPA_1-6) for lysophosphatidic acid, with a mixed depressive-anxiety phenotype. Dysfunctional social behaviors, which have been related to increased activation of the hypothalamus-pituitary-adrenal (HPA) axis, are key symptoms of depression and are even more prominent in patients with comorbid anxiety and depressive disorders. Social behavior and HPA functioning were assessed in animals lacking the LPA₁ receptor. For these purposes, we first examined social behaviors in wild-type and LPA₁ receptor-null mice. In addition, a dexamethasone (DEX) suppression test was carried out. maLPA₁-null mice exhibited social avoidance, a blunted response to DEX administration and an impaired circadian rhythm of corticosterone levels, which are features that are consistently dysregulated in many mental illnesses including anxious depression. Here, we have strengthened the previous experimental evidence for maLPA₁-null mice to represent a good animal model of anxious depression, providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, particularly this subtype of depression.