Repeated Experience of Aggression Changes in Gene Expression in the Hypothalamus in Male Mice of Two Strains

Abstract—Repeated fighting experiences can lead to changes in the neurophysiology and behavior of animals and to the formation of pathological aggression. Mechanisms of adaptation to repeated aggression are thought to be controlled through the hypothalamus and HPA axis. In this work, we studied the effect of repeated (30 days) experiences of aggression on gene expression in the hypothalamus in male mice of two strains, C57BL/6J and CD1. We measured the expression levels of the HPA axis genes (Crh, Crhr1, Crhbp, Fkbp5, and Nr3c1), as well as early response gene (Fos) and dopamine receptor D1 gene (Drd1). Repeated experiences of aggression led to prolongation of Fos activation in C57BL/6J, although the expression of other studied genes remained unchanged. CD1 aggressors are characterized by a decreased expression level of Crhr1 and Crhbp genes, whose products inhibit the secretion of corticotropin-releasing hormone. Most of the studied genes showed strain variation in gene expression that is probably associated with different levels of locomotor activity and anxiety in mice of these strains. The basal expression level of the Crh gene was higher in C57BL/6J mice, while the Crhr1, Crhbp, Fkbp5, Fos, and Drd1 genes were higher in CD1 mice. Thus, repeated experiences of aggression lead to gene expression changes in the hypothalamus of male mice, which depend on the genetic background and related psychophysiological features of individuals.