�������

Like humans, mice compete over territory and mates, and they also show increased confidence in their fighting skills the more they win. At first, a brain chemical called dopamine is essential for young males to master this behavior. But as they gain experience, the chemical grows 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, had until now been unclear.

In experiments in rodents, a team led by researchers at ������� Langone Health 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 for twice as long as they would have fought otherwise. When the cells were blocked, the novice mice did not fight at all.

In contrast, this pattern did not hold true in males that had extensive fighting experience. Whether or not dopamine-releasing cells were boosted or blocked, the duration of attack did not change. Notably, though, the more clashes a mouse won, the more fights it started in the future.

“Our findings offer new insight into how both nature and nurture shape aggression in males,” said study senior author “While aggression is an innate behavior, dopamine—and fighting experience—is essential for its maturation during adulthood,” added Dr. Lin, a professor in the Departments of and of at �����о��� Grossman School of Medicine.

A report on the findings was .

Building on their evidence for the role of dopamine in learning aggression, the authors set out to better understand the brain mechanisms that might explain it. 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 in such cases novice males never learned to fight, but those with previous fighting experience continued to engage in aggressive behavior. Similarly, promoting dopamine release in this area of the brain boosted hostility in rookies but had no effect on veterans.

This suggests that the lateral septum is a key brain site for dopamine to promote “aggression learning” in rodents and likely in other mammals, including people, says Dr. Lin, who is also a member of �����о��� Grossman School of Medicine’s .

The team also measured dopamine release in the lateral septum as the animals gained fighting experience. They found that the chemical surges the most on the day they first decide to attack. As mice become more experienced with fighting, this dopamine spike becomes less dramatic, supporting a central role of 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 did not affect aggressive behaviors in female mice in any way.

According to Dr. Lin, the results may offer new insight into addressing mental health conditions marked by intense 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 diseases, as well as to suppress violent behavior in psychiatric patients.

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

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

That said, Dr. Lin cautions that although mice share similar brain chemistry with people 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 medications in humans.

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

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

About ������� Langone Health

������� Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked ������� Langone the No. 1 comprehensive academic medical center in the country for three years in a row, and U.S. News & World Report recently placed nine of its clinical specialties among the top five in the nation. ������� Langone offers a comprehensive range of medical services with one high standard of care across 6 inpatient locations, its Perlmutter Cancer Center, and more than 300 outpatient locations in the New York area and Florida. With $14.2 billion in revenue this year, the system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise with over $1 billion in active awards from the National Institutes of Health.

Media Inquiries

Shira Polan
Phone: 212-404-4279
Shira.Polan@�������Langone.org