Handling, genetic and housing effects on the mouse stress system, dopamine function, and behavior.

This research was designed to examine how early stimulation (i.e., handling), subsequent housing conditions and genetic factors interact to produce adult differences in stress regulation. High-aggressive (NC900) and low-aggressive (NC100) mice were handled for 3 weeks potspartum and were subsequently isolated or grouped until observed as adults in an open field or a dyadic test. In NC100, handling abolished the temporal variations seen in open-field activity among the nonhandled subjects and reduced corticosterone (CORT) activation. In NC900, these two measures were unaffected by handling. Only among handled NC100 did subsequent group rearing further reduce CORT activation. By contrast, handling caused an up-regulation of D1 dopamine receptors in both lines, and, in NC100, this effect was increased by group rearing. In a dyadic encounter with another male mouse, subjects of both lines showed handling effects. NC100 froze less rapidly and NC900 attacked more rapidly. This multifactorial design showed that the systemic effects of handling are modulated by genetic background, and that measures of these effects are affected by experience beyond infancy. Our findings also showed that the effects of handling vary when assessed across different physiological systems and across social and nonsocial testing conditions.