Early postnatal events exert powerful effects on development, inducing persistent functional alterations in different brain network, such as the catecholamine prefrontal–accumbal system, and increasing the risk of developing psychiatric disorders later in life. However, a vast body of literature shows that the interaction between genetic factors and early environmental conditions is crucial for expression of psychopathologies in adulthood. We evaluated the long-lasting effects of a repeated cross-fostering (RCF) procedure in 2 inbred strains of mice (C57BL/6J, DBA/2), known to show a different susceptibility to the development and expression of stress-induced psychopathologies. Coping behavior (forced swimming test) and preference for a natural reinforcing stimulus (saccharine preference test) were assessed in adult female mice of both genotypes. Moreover, c-Fos stress-induced activity was assessed in different brain regions involved in stress response. In addition, we evaluated the enduring effects of RCF on catecholamine prefrontal–accumbal response to acute stress (restraint) using, for the first time, a new “dual probes” in vivo microdialysis procedure in mouse. RCF experience affects behavioral and neurochemical responses to acute stress in adulthood in opposite direction in the 2 genotypes, leading DBA mice toward an “anhedonic-like” phenotype and C57 mice toward an increased sensitivity for a natural reinforcing stimulus.