Experience-dependent dopamine modulation of male aggression

Bing Dai (), Bingqin Zheng, Xiuzhi Dai, Xiaoyang Cui, Luping Yin, Jing Cai, Yizhou Zhuo, Nicolas X. Tritsch, Larry S. Zweifel, Yulong Li and Dayu Lin ()
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Bing Dai: New York University Grossman School of Medicine
Bingqin Zheng: New York University Grossman School of Medicine
Xiuzhi Dai: New York University Grossman School of Medicine
Xiaoyang Cui: New York University Grossman School of Medicine
Luping Yin: New York University Grossman School of Medicine
Jing Cai: New York University Grossman School of Medicine
Yizhou Zhuo: Peking University School of Life Sciences
Nicolas X. Tritsch: New York University Grossman School of Medicine
Larry S. Zweifel: University of Washington
Yulong Li: Peking University School of Life Sciences
Dayu Lin: New York University Grossman School of Medicine

Nature, 2025, vol. 639, issue 8054, 430-437

Abstract: Abstract Numerous studies support the role of dopamine in modulating aggression1,2, 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 dopaminergic cells strongly influence aggression in novice aggressors, they become ineffective in expert aggressors. Furthermore, eliminating 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 aggression control. Dopamine enables the flow of information from the hippocampus to the dLS by weakening local inhibition in novice aggressors. In expert aggressors, dLS local inhibition naturally weakens, and the ability of dopamine to modulate dLS cells diminishes. Overall, these results reveal a sophisticated role of dopamine in the rise of aggression in adult male mice.

Date: 2025
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DOI: 10.1038/s41586-024-08459-w

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