Here, we used Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the Tph2 to investigate the effects of provoked 5-HT deficiency in the modulation of emotional responses and risk for anxiety disorders and depression in interaction with environmental adversity during brain maturation in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). This evidence concerns the gene TPH2 and major depressive disorder.