Mice, much like humans, engage in competition for territory and mates, gaining confidence in their fighting abilities as they achieve victories. Initially, a brain chemical known as dopamine is crucial for young males to learn these behaviors. However, a recent study indicates that as they gain experience, dopamine becomes less significant in driving aggressive tendencies.
Dopamine has long been associated with male aggression, but the role of prior experiences in this dynamic has remained largely unexplored until now.
In rodent experiments, researchers from NYU Langone Health enhanced the activity of dopamine-releasing neurons in the ventral tegmental area of the brain. This manipulation resulted in inexperienced male fighters attacking for twice the normal duration. When these dopamine cells were inhibited, the novice mice exhibited no fighting behavior whatsoever.
In contrast, this pattern changed for males with significant fighting experience. Regardless of whether dopamine activity was increased or decreased, the length of their attacks remained constant. Notably, as mice won more fights, they initiated future confrontations more frequently.
“Our research provides fresh perspectives on how both instinct and experiences influence male aggression,” stated Dr. Dayu Lin, the study’s senior author. “While aggression is a natural behavior, dopamine—and the experience of fighting—plays a critical role in its development during adulthood,” explained Lin, who is a professor in the Departments of Psychiatry and Neuroscience at NYU Grossman School of Medicine.
The findings will be published online on January 22 in the journal Nature.
Building on their insights into dopamine’s role in aggressive behavior, the researchers aimed to delve deeper into the brain mechanisms behind it. They inhibited dopamine release from neurons in the ventral tegmental area to the lateral septum, a region linked to aggression regulation. This intervention showed that novice males were unable to learn fighting skills, whereas those with prior fighting experience maintained aggressive behavior. Similarly, enhancing dopamine release in this brain area increased hostility in inexperienced fighters, but had no impact on veterans.
This underscores the importance of the lateral septum as a key brain region where dopamine facilitates “aggression learning” in rodents and likely in other mammals, including humans, according to Lin, who is also affiliated with the Institute for Translational Neuroscience at NYU Grossman School of Medicine.
The team subsequently measured dopamine release in the lateral septum as the mice gained fighting experience. They discovered that dopamine levels surged on the day the animals first chose to fight. As their fighting experience grew, these dopamine spikes became less pronounced, reinforcing the idea that dopamine is crucial for initial aggression learning.
Importantly, the researchers found that dopamine did not influence aggression in female mice. Adjusting dopamine levels did not alter aggressive behavior in the females at all.
Lin suggests that these results could provide fresh insights into treating mental health disorders characterized by severe mood and behavioral fluctuations, like schizophrenia, bipolar disorder, and borderline personality disorder. Antipsychotic medications that block dopamine release are frequently used in managing such conditions and curbing violent tendencies in psychiatric patients.
“Our findings indicate that targeting dopamine may not be helpful for individuals with a long-standing history of aggression,” noted Lin. “Thus, healthcare providers should take into account a patient’s aggressiveness history, along with factors like age and gender, when determining treatment options.”
Lin further explains that the findings might clarify why antipsychotic medications seem to have a stronger and more prolonged effect in children than in adults, as aggression often resurfaces in adults after stopping the treatment.
Nevertheless, Lin warns that while there are similarities in brain chemistry between mice and humans, future research is necessary to fully understand how past behaviors might influence the effectiveness of antipsychotic treatments in human populations.
This study was funded by several grants from the National Institutes of Health, including R01MH101377, R01MH124927, U19NS107616, U01NS11335, U01NS12082, P30DA048736, and R01MH133669. Additionally, support for further research was provided by the Vulnerable Brain Project.
Along with Lin, other researchers from NYU Langone who contributed to the study include Bingqin Zheng, MS; Xiuzhi Dai; Xiaoyang Cui, BS; Luping Yin, PhD; Jing Cai, PhD; and Nicolas Tritsch, PhD. Collaborators also included Yizhou Zhuo, PhD, and Yulong Li, PhD, from the Peking University School of Life Sciences in Beijing, as well as Larry Zweifel, PhD, from the University of Washington in Seattle. Bing Dai, PhD, a former graduate student at NYU Langone and currently a postdoctoral associate at the Massachusetts Institute of Technology, served as the lead author of the study.
