Enhancement of Aggression Induced by Isolation Rearing is Associated with a Lack of Central Serotonin

  • Yiqiong Liu
  • Yunong Sun
  • Xiaoyan Zhao
  • Ji-Young Kim
  • Lu Luo
  • Qian Wang
  • Xiaolu Meng
  • Yonghui Li
  • Nan Sui
  • Zhou-Feng Chen
  • Chuxiong Pan
  • Liang LiEmail author
  • Yan ZhangEmail author
Original Article


Isolation rearing (IR) enhances aggressive behavior, and the central serotonin (5-hydroxytryptamine, 5-HT) system has been linked to IR-induced aggression. However, whether the alteration of central serotonin is the cause or consequence of enhanced aggression is still unknown. In the present study, using mice deficient in central serotonin Tph2−/− and Lmx1b−/−, we examined the association between central serotonin and aggression with or without social isolation. We demonstrated that central serotonergic neurons are critical for the enhanced aggression after IR. 5-HT depletion in wild-type mice increased aggression. On the other hand, application of 5-HT in Lmx1b−/− mice inhibited the enhancement of aggression under social isolation conditions. Dopamine was downregulated in Lmx1b−/− mice. Similar to 5-HT, L-DOPA decreased aggression in Lmx1b−/− mice. Our results link the serotoninergic system directly to aggression and this may have clinical implications for aggression-related human conditions.


5-HT Aggression Social isolation Dopamine Lmx1b 



We thank Dr. Jian-Xu Zhang (Institute of Zoology, Chinese Academy of Sciences) and Dr. Yan Liu (Peking University) for reading the manuscript and helpful suggestions. This work was supported by the National Natural Science Foundation of China (81425009, 31630028, 91632305, 30950030, 31170988, and 81671044), and the National Basic Research Development Program (973 Program) of China (2009CB522002).

Conflicts of interest

The authors declare no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the work submitted that could inappropriately influence (bias) their work.

Supplementary material

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Supplementary material 1 (PDF 492 kb)


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Yiqiong Liu
    • 1
    • 8
  • Yunong Sun
    • 7
  • Xiaoyan Zhao
    • 2
  • Ji-Young Kim
    • 3
  • Lu Luo
    • 4
  • Qian Wang
    • 4
  • Xiaolu Meng
    • 6
  • Yonghui Li
    • 6
  • Nan Sui
    • 6
  • Zhou-Feng Chen
    • 3
  • Chuxiong Pan
    • 2
  • Liang Li
    • 4
    • 5
    Email author
  • Yan Zhang
    • 1
    • 8
    Email author
  1. 1.State Key Laboratory of Membrane Biology, College of Life SciencesPeking UniversityBeijingChina
  2. 2.Department of Anesthesiology, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
  3. 3.Department of Anesthesiology, Department of Psychiatry, Department of Developmental Biology, Center for the Study of ItchWashington University School of MedicineSaint LouisUSA
  4. 4.School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental HealthPeking UniversityBeijingChina
  5. 5.Beijing Institute for Brain DisordersBeijingChina
  6. 6.Key Laboratory of Mental Health, Institute of PsychologyChinese Academy of SciencesBeijingChina
  7. 7.Hendrix CollegeConwayUSA
  8. 8.PKU-IDG/McGovern Institute for Brain ResearchBeijingChina

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