Dopamine stimulates the learning of aggression in men

Summary : New research reveals that dopamine plays a crucial role in learning to fight in young male mice, with the influence of the chemical diminishing as they gain experience. In beginning fighters, increasing dopamine increased aggression, while blocking it prevented them from fighting.

However, experienced fighters showed no behavioral changes regardless of dopamine manipulation, highlighting the role of experience in shaping aggression. The study identifies the lateral septum as a key brain region for “aggression learning” in men, but no similar effects were observed in women.

Key facts:

• The role of dopamine: Dopamine promotes aggression in novice male mice but becomes less influential with experience.
• Brain region identified: The lateral septum mediates the effects of dopamine on aggression learning in males.
• Gender differences: Manipulating dopamine did not impact aggressive behaviors in female mice.

Source: NYU Langone

Like humans, mice compete for territory and mates, and show increased confidence in their fighting abilities as they win. Initially, 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, according to a new study.

Dopamine has been associated with male aggression for decades. However, until now it has been unclear how past experiences might influence this relationship.

In rodent experiments, a team led by NYU Langone Health researchers stimulated the activity of dopamine-releasing cells in a part of the brain called the ventral tegmental area.

The results revealed that in inexperienced male fighters, this led the animals to attack for twice as long as if they were fighting naturally. When the cells were blocked, the novice mice didn’t fight at all.

In contrast, this pattern did not apply to men with extensive combat experience. Whether or not the dopamine-releasing cells were stimulated or blocked, the duration of the attack did not change. However, the more fights a mouse won, the more fights it would initiate in the future.

“Our findings offer new insights into how ‘nature’ and ‘nurture’ shape aggression in men,” said Dayu Lin, PhD, lead author of the study.

“Although aggression is an innate behavior, dopamine – and combat experience – are essential for its maturation into adulthood,” added Lin, a professor in the departments of psychiatry and neuroscience at the NYU Grossman School of Medicine.

A report on the results is published online January 22 in the journal Nature.

Building on their evidence of the role of dopamine in learning aggression, the authors set out to better understand the brain mechanisms that could explain it. To do this, the team stopped cells in the ventral tegmental area of ​​the brain from releasing dopamine in another region called the lateral septum, a site known to regulate aggression.

They found that novice males would never learn to fight, but those with combat experience would continue to exhibit aggressive behavior. Similarly, promoting dopamine release in this area of ​​the brain stimulated hostility in recruits 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 other mammals, including humans, says Lin, who is also a member of the Translational Neuroscience Institute at NYU Grossman School of Medicine.

The team also measured dopamine release in the lateral septum as the animals gained combat experience. They found that the chemical increases the most on the day they decide to attack for the first time.

As the mouse becomes more experienced in fighting, this dopamine spike becomes less dramatic, confirming the chemical’s central role in the initial learning of aggression.

Importantly, researchers also found that dopamine did not appear to play a similar role in female aggression. In fact, manipulating dopamine levels did not affect the aggressive behaviors of female mice in any way.

According to Lin, the findings could offer new insights in combating mental health problems marked by intense changes in mood and behavior, such as schizophrenia, bipolar disorder and borderline personality disorder.

Antipsychotic medications that interfere with dopamine release are commonly used to treat these illnesses, as well as to suppress violent behavior in psychiatric patients.

“Our results suggest that targeting dopamine may not be an effective tool for treating people with a long history of aggression,” Lin said.

“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 findings may also explain why antipsychotic medications are known to have a stronger, longer-lasting effect in children than in adults, for whom aggression often returns once they stop receiving medication.

That said, Lin cautions that even though mice share similar brain chemistry to humans and the current findings echo human clinical findings, additional research will be needed to demonstrate the impact of past behavior on drug effectiveness. antipsychotics in humans.

Funding: 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 Lin, other NYU Langone researchers involved in the study are Bingqin Zheng, MS; Xiuzhi Dai; Xiaoyang Cui, B.S.; Luping Yin, PhD; Jing Cai, Ph.D.; and Nicolas Tritsch, PhD.

Other researchers on the study include Yizhou Zhuo, PhD, and Yulong Li, PhD, of the School of Life Sciences at Peking University in Beijing; and Larry Zweifel, PhD, of the University of Washington in Seattle. Bing Dai, PhD, a former graduate student at NYU Langone and current postdoctoral associate at the Massachusetts Institute of Technology in Cambridge, was the lead author of the study.

About this news from research on aggression and neuroscience

Author: Shira Polan
Source: NYU Langone
Contact: Shira Polan – NYU Langone
Picture: Image is credited to Neuroscience News

Original research: Closed access.
“Experience-dependent dopaminergic modulation of male aggression” by Dayu Lin et al. Nature

---

Abstract

Dopaminergic modulation dependent on the experience of male aggression

Many studies support the role of dopamine in modulating aggression, but the exact neural mechanisms remain elusive. Here we show that dopaminergic cells in the ventral tegmental area (VTA) can bidirectionally modulate aggression in male mice in an experience-dependent manner.

Although VTA dopamine cells strongly influence aggression in novice aggressors, they become ineffective in expert aggressors. Furthermore, elimination of dopamine synthesis in the VTA prevents the emergence of aggression in naive mice but leaves aggression intact in expert aggressors. VTA dopamine modulates aggression through the dorsal lateral septum (dLS), a region known for its control of aggression.

Dopamine allows information flow from the hippocampus to the dLS by weakening local inhibition in novice aggressors. In expert aggressors, local inhibition of dLS naturally weakens and the ability of dopamine to modulate dLS cells diminishes.

Overall, these results reveal a sophisticated role for dopamine in increasing aggression in adult male mice.