The study offers new insights into the nature and nurture of aggression in men

The study offers new insights into the nature and nurture of aggression in men

Like humans, mice will compete for territory and mates and show increased confidence in their fighting abilities the more they win. First, a brain chemical called dopamine is essential for young men to master this behavior. But as they gain experience, the chemical becomes less important in promoting aggression, a new study shows.

Dopamine has been linked to male aggression for decades. However, how previous experiences might influence this relationship had previously been unclear.

In experiments with rodents, a team of researchers at NYU Langone Health increased activity in dopamine-releasing cells in a part of the brain called the ventral tegmental area. The results showed that in inexperienced male fighters, the animals continued to attack for twice as long as they would have fought naturally. When the cells were blocked, the novice mice didn't fight at all.

In contrast, this pattern did not hold true for men who had extensive combat experience. Regardless of whether dopamine-releasing cells were boosted or blocked, the duration of the attack did not change. The more a mouse talks together, the more fights they would start in the future.

Our findings offer new insights into the ways in which both nature and “nurture aggression in men.” While aggression is an innate behavior, dopamine – and combat experience – are essential to its maturation into adulthood. “

Dayu Lin, PhD, senior author, professor in the departments of psychiatry and neuroscience, NYU Grossman School of Medicine

A report on the findings will be published online January 22 in the journalNature.

Building on their evidence for dopamine's role in learning aggression, the authors wanted to better understand the brain mechanisms that might explain this. To do this, the team prevented cells in the ventral tegmental area of ​​the brain from releasing dopamine into another region called the lateral septum, a site known to regulate aggression. They found that beginners will never learn. Similarly, promoting dopamine release in this area of ​​the brain increased hostility in newcomers but had no effect on veterans.

This suggests that the lateral septum is an important brain site for dopamine to promote "aggression learning" in rodents and likely other mammals, including humans, says Lin, who is also a member of NYU Grossman School of Medicine's Institute for Translational Neuroscience.

The team also measured dopamine release in the lateral septum as the animals gained fighting experience. They found that chemical increases peaked the most on the day they first attacked. As the mouse becomes more experienced with fighting, this dopamine spike becomes less dramatic, supporting a central role for the chemical in initial aggression learning.

Importantly, the researchers also found that dopamine did not appear to play a similar role in female aggression. In fact, manipulating dopamine levels in no way caused aggressive behaviors in female mice.

Lin said the findings may provide new insights into combating mental illnesses characterized by intense changes in mood and behavior, such as schizophrenia, bipolar disorder and borderline personality disorder. Antipsychotics that impair dopamine release are commonly used to treat such illnesses as well as to suppress violent behavior in psychiatric patients.

"Our results suggest that targeting dopamine may not be an effective tool in treating those with a long history of aggression," Lin said. "As a result, healthcare providers may need to consider a patient's medical history, as well as their age and gender, when considering which therapy to use."

Lin adds that the findings may also explain why antipsychotics have a stronger and longer-lasting effect in children than in adults, for whom aggression often returns once they stop taking medication.

However, LIN warns that while mice have similar brain chemistry to humans and that the current results reflect human clinical findings, more research will be needed to demonstrate the effects of prior behavior on the effectiveness of antipsychotics in humans.

Funding for the study was provided by National Institutes of Health Grants R01MH101377, R01MH124927, U19NS107616, U01NS11335, U01NS12082, P30DA048736, and R01MH133669. Additional study funding was provided by the Endangered Brain Project.

In addition to Lin, other participants in the study include NYU Langone researchers Bingqin Zheng, MS; Xiuzhi Dai; Xiaoyang Cui, BS; Luping Yin, PhD; Jing Cai, PhD; and Nicolas Tritsch, PhD. Additional study investigators include Yizhou Zhuo, PhD, and Yulong Li, PhD, at Peking University School of Life Sciences in Beijing; and Larry Doubt, PhD, at the University of Washington in Seattle. Bing Dai, PhD, a former graduate student at NYU Langone and current postdoctoral fellow at the Massachusetts Institute of Technology in Cambridge, was lead author.

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