Brain Mechanism of Aggression

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During the funding period, we have worked to determine the role of estrogen receptor β (ER-β) in the regulation of aggressive behavior in mice in relation to the levels of anxiety levels, social recognition and stress responsiveness.(1) In the first set of the studies, we tested the effects of estrogen replacement on the levels of anxiety in gonadectomized male mice of ER-b knockout (βERKO) as well as wild-type (WT). The levels of anxiety measured during the light-dark transition tests significantly decreased by estrogen treatment in WT, but not in βERKO, male mice. We also measured the mRNA levels of serotonin transporter (SERT) in ER-β rich midbrain dorsal raphe nuclei. Again, estrogen increased SERT mRNA levels in WT mice but it failed to do so in βERKO mice.(2) Aggressive behavior of male mice is known to first appear around the time of puberty onset at 5-6weeks of age. In our previous studies, we found an increase of aggression in PERKO mice at the pubertal age suggesting disruption of inhibitory brain system. In the second set of studies, we studied the effects of stress loading on the onset of aggressive behavior around the puberty age. Aggressive behavior measured at 5weeks of age was greatly decreased in mice those separated from their mothers during neonatal period. Decreased levels and a delayed onset of aggression at pubertal age were particularly pronounced in βERKO male mice compared to WT mice. Therefore, we concluded that ER-β might be involved in the development of stress responsiveness around the time of pubertal onset of aggression.