Early-life stress of maternal separation (MS) during postnatal days 2 to 14 (P2- 14) in mice produces anxiety and depressive-like symptoms in adulthood. Emotional alterations are accompanied by alteration in prefrontal cortico-limbic pathways involved in mood control. The serotonin (5-HT) system plays a key role in the MS model, however the specific participation of 5-HT7 receptors in the manifestation of the adult anxiety and depressive-like symptoms remains unknown. In this study, cohorts of mice were exposed to MS during P2-14 while administering a selective 5-HT7 receptor antagonist (SB-269970, s.c. 20mg/kg/day) and their respective controls. We assessed in adulthood anxiety and depressive-like behaviors in all our experimental groups. The results evidence a key role of 5-HT7 receptors in the early-life vulnerability to stress resulting in adult predisposition to develop emotional alterations of relevance to mental disorders.