The study offers new insight into how nature and nurture shape aggression in males

Like humans, mice will fight over territory and mates and show increased confidence in their abilities for more winning battles. First, a brain chemical called dopamine is necessary 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. How past experiences might influence this relationship, however, has until now been unclear.

In experiments on rodents, a team led by NYU Langone Health researchers boosted activity in dopamine-releasing cells in a part of the brain called the ventral tegmental area. The findings revealed that in inexperienced male fighters, this led the animals to attack twice as often as they would have fought naturally. When the cells were blocked, the novice mice would not fight at all.

In contrast, this pattern did not hold in males who had extensive combat experience. Whether the dopamine-releasing cells were enhanced or blocked, the duration of the attack did not change. But specifically, the more fights a mouse won, the more fights they would start in the future.

Our findings offer new insight into how both ‘nature’ and ‘nurture’ shape aggression in males. While aggression is an innate behavior, dopamine—and the experience of fighting—is essential for its maturation into adulthood. “

Dayu Lin, PhD, Study Senior Author, Professor in the Departments of Psychiatry and Neuroscience, NYU Grossman School of Medicine

A report on the findings is published online Jan. 22 in the journal Nature.

Building on their evidence of dopamine’s role in aggression learning, the authors want to better understand the brain mechanisms that could explain it. To do this, the team prevented cells in the ventral region of the brain from releasing dopamine into another area called the parietal lobe, a space known to regulate aggression. They found that novice males will never learn to fight, but those with prior fighting experience will continue to engage in aggressive behavior. Similarly, promoting dopamine release in this brain region enhanced hostility in recruits but had no effect in veterans.

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

The team also measured the release of dopamine in the lateral septum as the animals gained combat experience. They found that the chemical increases the most on the day they first decide to attack. 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 does not appear to play a similar role in female aggression. In fact, manipulating dopamine levels did not in any way affect aggressive behaviors in female mice.

According to Lin, the results may offer new insight into the treatment of mental health conditions characterized by marked shifts in mood and behavior, such as schizophrenia, bipolar disorder and borderline personality disorder. Antipsychotic drugs that interfere with 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 when dealing with those with a long history of aggression,” said Lin. “As a result, health care providers may need to consider a patient’s history, as well as their age and gender, when considering which treatment to use.”

Lin adds that the results may also explain why antipsychotic drugs are known to have a stronger and longer-lasting effect on children than on adults, for whom aggression often returns once they stop taking medication.

That said, Lin cautions that while mice share similar brain chemistry to humans and that the current findings echo human clinical results, more research will be needed to demonstrate the impact of past behavior on the effectiveness of antipsychotic drugs in humans.

Funding for the study was provided by National Institutes of Health R01MH101377, R01MH124927, U19NS107616, U01NS11335, U01NS12082, P30DA048736, and R01MH13669. Further study funding is provided by the vulnerable brain project.

In addition to Lin, other NYU Langone researchers involved in the study are Bingqin Zheng, MS; Xiuzhi dai? Xiaoyang Cui, BS; Luping Yin, PhD; Jing Cai, PhD. and Nicolas Tritsch, PhD. Other study investigators include Yizhou Zhuo, PhD, and Yulong Li, PhD, at the Peking University School of Science in Beijing. and Larry Zweifel, PhD, at the University of Washington in Seattle. Bing Dai, PhD, a former graduate student at NYU Langone and a current postdoctoral fellow at the Massachusetts Institute of Technology in Cambridge, served as lead author of the study.