The balance between mesocortical and mesoaccumbens dopamine (DA) response to stress may represent a major diathesis in psychopathology. These experiments evaluated the influence of variable living conditions on this phenotype and on behavioral coping. Mesocortical and mesoaccumbens DA responses to stress challenge (restraint) were analyzed in individually housed or food restricted mice of an inbred strain to control for genotype-dependent variability. Mice housed in groups with free access to food were used as controls. Little or no differences among the three conditions were found for basal mesoaccumbens and mesocortical DA and metabolite levels. Stress challenge promoted parallel activation of mesocortical and mesoaccumbens DA metabolism and release in group-housed mice. Individually housed mice showed enhanced mesocortical and reduced mesoaccumbens response to stress challenge. Instead, food restricted mice showed no response by the mesocortical DA system and enhanced mesoaccumbens DA response. Finally, the two differential housing conditions promoted opposite alterations of the behavioral profile exhibited by mice exposed to the forced swimming test. These results indicate opposite imbalances between mesocortical and mesoaccumbens DA responses to stress in intact, drug-naive animals, point to a strict relationship between these unbalanced responses and behavioral coping with aversive events and indicate that central and behavioral responses to stress are highly dependent on individual experiences.