Advertisement

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

Abstract

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.

Keywords

5-HT Aggression Social isolation Dopamine Lmx1b 

Notes

Acknowledgements

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

12264_2019_373_MOESM1_ESM.pdf (492 kb)
Supplementary material 1 (PDF 492 kb)

References

  1. 1.
    Waider J, Araragi N, Gutknecht L, Lesch KP. Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology 2011, 36: 393–405.CrossRefGoogle Scholar
  2. 2.
    Olivier B. Serotonin: A never-ending story. Eur J Pharmacol 2015, 753: 2–18.CrossRefGoogle Scholar
  3. 3.
    Bell R, Hobson H. 5-HT1A receptor influences on rodent social and agonistic behavior: a review and empirical study. Neurosci Biobehav Rev 1994, 18: 325–338.CrossRefGoogle Scholar
  4. 4.
    Dolan M, Deakin WJ, Roberts N, Anderson I. Serotonergic and cognitive impairment in impulsive aggressive personality disordered offenders: are there implications for treatment? Psychol Med 2002, 32: 105–117.CrossRefGoogle Scholar
  5. 5.
    Coccaro EF, Lee R, Kavoussi RJ. Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology 2010, 35: 435–444.CrossRefGoogle Scholar
  6. 6.
    Russo S, Kema IP, Bosker F, Haavik J, Korf J. Tryptophan as an evolutionarily conserved signal to brain serotonin: molecular evidence and psychiatric implications. World J Biol Psychiatry 2009, 10: 258–268.CrossRefGoogle Scholar
  7. 7.
    McCloskey MS, Ben-Zeev D, Lee R, Berman ME, Coccaro EF. Acute tryptophan depletion and self-injurious behavior in aggressive patients and healthy volunteers. Psychopharmacology (Berl) 2009, 203: 53–61.CrossRefGoogle Scholar
  8. 8.
    Lanctot KL, Herrmann N, Eryavec G, van Reekum R, Reed K, Naranjo CA. Central serotonergic activity is related to the aggressive behaviors of Alzheimer’s disease. Neuropsychopharmacology 2002, 27: 646–654.Google Scholar
  9. 9.
    Suri D, Teixeira CM, Cagliostro MKC, Mahadevia D, Ansorge MS. Monoamine–sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology 2015, 40: 88–112.CrossRefGoogle Scholar
  10. 10.
    Rosell DR, Thompson JL, Slifstein M, Xu X, Frankle WG, New AS, et al. Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry 2010, 67: 1154–1162.CrossRefGoogle Scholar
  11. 11.
    Soloff PH, Chiappetta L, Mason NS, Becker C, Price JC. Effects of serotonin-2A receptor binding and gender on personality traits and suicidal behavior in borderline personality disorder. Psychiatry Res Neuroimaging 2014, 222: 140–148.CrossRefGoogle Scholar
  12. 12.
    Silva H, Iturra P, Solari A, Villarroel J, Jerez S, Jimenez M, et al. Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder. Psychiatr Genet 2010, 20: 25–30.CrossRefGoogle Scholar
  13. 13.
    Bortolato M, Pivac N, Muck Seler D, Nikolac Perkovic M, Pessia M, Di Giovanni G. The role of the serotonergic system at the interface of aggression and suicide. Neuroscience 2013, 236: 160–185.CrossRefGoogle Scholar
  14. 14.
    Stadler C, Zepf FD, Demisch L, Schmitt M, Landgraf M, Poustka F. Influence of rapid tryptophan depletion on laboratory-provoked aggression in children with ADHD. Neuropsychobiology 2007, 56: 104–110.CrossRefGoogle Scholar
  15. 15.
    Kotting WF, Bubenzer S, Helmbold K, Eisert A, Gaber TJ, Zepf FD. Effects of tryptophan depletion on reactive aggression and aggressive decision-making in young people with ADHD. Acta Psychiatr Scand 2013, 128: 114–123.CrossRefGoogle Scholar
  16. 16.
    Barkan T, Peled A, Modai I, Barak P, Weizman A, Rehavi M. Serotonin transporter characteristics in lymphocytes and platelets of male aggressive schizophrenia patients compared to non-aggressive schizophrenia patients. Eur Neuropsychopharmacol 2006, 16: 572–579.CrossRefGoogle Scholar
  17. 17.
    Frisch A, Finkel B, Michaelovsky E, Sigal M, Laor N, Weizman R. A rare short allele of the serotonin transporter promoter region (5-HTTLPR) found in an aggressive schizophrenic patient of Jewish Libyan origin. Psychiatr Genet 2000, 10: 179–183.CrossRefGoogle Scholar
  18. 18.
    Steinert T HK. External validity of studies on aggressive behavior in patients with schizophrenia: systematic review. Clin Pract Epidemiol Ment Health 2012, 8: 74–80.CrossRefGoogle Scholar
  19. 19.
    Linnoila VM, Virkkunen M. Aggression, suicidality, and serotonin. J Clin Psychiatry 1992, 53 Suppl: 46–51.Google Scholar
  20. 20.
    Miczek KA, Fish EW, De Bold JF, De Almeida RM. Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems. Psychopharmacology (Berl) 2002, 163: 434–458.CrossRefGoogle Scholar
  21. 21.
    Veenema AH. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models? Front Neuroendocrinol 2009, 30: 497–518.CrossRefGoogle Scholar
  22. 22.
    Westergaard GC, Suomi SJ, Higley JD, Mehlman PT. CSF 5-HIAA and aggression in female macaque monkeys: species and interindividual differences. Psychopharmacology (Berl) 1999, 146: 440–446.CrossRefGoogle Scholar
  23. 23.
    Shannon C, Schwandt ML, Champoux M, Shoaf SE, Suomi SJ, Linnoila M, et al. Maternal absence and stability of individual differences in CSF 5-HIAA concentrations in rhesus monkey infants. Am J Psychiatry 2005, 162: 1658–1664.CrossRefGoogle Scholar
  24. 24.
    Shrestha SS, Nelson EE, Liow JS, Gladding R, Lyoo CH, Noble PL, et al. Fluoxetine administered to Juvenile monkeys: effects on the serotonin transporter and behavior. Am J Psychiatry 2014, 171: 323–331.CrossRefGoogle Scholar
  25. 25.
    Higley JD, King ST Jr., Hasert MF, Champoux M, Suomi SJ, Linnoila M. Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behavior in rhesus macaque females. Neuropsychopharmacology 1996, 14: 67–76.CrossRefGoogle Scholar
  26. 26.
    Higley JD, Mehlman PT, Higley SB, Fernald B, Vickers J, Lindell SG, et al. Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Arch Gen Psychiatry 1996, 53: 537–543.CrossRefGoogle Scholar
  27. 27.
    Veenema AH, Blume A, Niederle D, Buwalda B, Neumann ID. Effects of early life stress on adult male aggression and hypothalamic vasopressin and serotonin. Eur J Neurosci 2006, 24: 1711–1720.CrossRefGoogle Scholar
  28. 28.
    Diamantopoulou A, Raftogianni A, Stamatakis A, Alikaridis F, Oitzl MS, Stylianopoulou F. Denial of reward in the neonate shapes sociability and serotonergic activity in the adult rat. PLoS One 2012, 7: e33793.CrossRefGoogle Scholar
  29. 29.
    Whitaker-Azmitia P, Zhou F, Hobin J, Borella A. Isolation-rearing of rats produces deficits as adults in the serotonergic innervation of hippocampus. Peptides 2000, 21: 1755–1759.CrossRefGoogle Scholar
  30. 30.
    Heidbreder CA, Weiss IC, Domeney AM, Pryce C, Homberg J, Hedou G, et al. Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome. Neuroscience 2000, 100: 749–768.CrossRefGoogle Scholar
  31. 31.
    Soga T, Teo CH, Cham KL, Idris MM, Parhar IS. Early-life social isolation impairs the gonadotropin-inhibitory hormone neuronal activity and serotonergic system in male rats. Front Endocrinol (Lausanne) 2015, 6: 172.CrossRefGoogle Scholar
  32. 32.
    Dalley JW, Theobald DE, Pereira EA, Li PM, Robbins TW. Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity. Psychopharmacology (Berl) 2002, 164: 329–340.CrossRefGoogle Scholar
  33. 33.
    Miura H, Qiao H, Ohta T. Attenuating effects of the isolated rearing condition on increased brain serotonin and dopamine turnover elicited by novelty stress. Brain Res 2002, 926: 10–17.CrossRefGoogle Scholar
  34. 34.
    Yorgason JT, Calipari ES, Ferris MJ, Karkhanis AN, Fordahl SC, Weiner JL, et al. Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum. Neuropharmacology 2016, 101: 471–479.CrossRefGoogle Scholar
  35. 35.
    Han X, Wang W, Shao F, Li N. Isolation rearing alters social behaviors and monoamine neurotransmission in the medial prefrontal cortex and nucleus accumbens of adult rats. Brain Res 2011, 1385: 175–181.CrossRefGoogle Scholar
  36. 36.
    Weiss IC, Domeney AM, Moreau JL, Russig H, Feldon J. Dissociation between the effects of pre-weaning and/or post-weaning social isolation on prepulse inhibition and latent inhibition in adult Sprague–Dawley rats. Behav Brain Res 2001, 121: 207–218.CrossRefGoogle Scholar
  37. 37.
    Kosten TA, Kim JJ, Lee HJ. Early life manipulations alter learning and memory in rats. Neurosci Biobehav Rev 2012, 36: 1985–2006.CrossRefGoogle Scholar
  38. 38.
    Matsumoto K, Uzunova V, Pinna G, Taki K, Uzunov DP, Watanabe H, et al. Permissive role of brain allopregnanolone content in the regulation of pentobarbital-induced righting reflex loss. Neuropharmacology 1999, 38: 955–963.CrossRefGoogle Scholar
  39. 39.
    Guidotti A, Dong E, Matsumoto K, Pinna G, Rasmusson AM, Costa E. The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders. Brain Res Brain Res Rev 2001, 37: 110–115.CrossRefGoogle Scholar
  40. 40.
    Koike H, Ibi D, Mizoguchi H, Nagai T, Nitta A, Takuma K, et al. Behavioral abnormality and pharmacologic response in social isolation-reared mice. Behav Brain Res 2009, 202: 114–121.CrossRefGoogle Scholar
  41. 41.
    Toth M, Halasz J, Mikics E, Barsy B, Haller J. Early social deprivation induces disturbed social communication and violent aggression in adulthood. Behav Neurosci 2008, 122: 849–854.CrossRefGoogle Scholar
  42. 42.
    Wongwitdecha N, Marsden CA. Social isolation increases aggressive behaviour and alters the effects of diazepam in the rat social interaction test. Behav Brain Res 1996, 75: 27–32.CrossRefGoogle Scholar
  43. 43.
    Arakawa H. Interaction between isolation rearing and social development on exploratory behavior in male rats. Behav Processes 2005, 70: 223–234.CrossRefGoogle Scholar
  44. 44.
    Paulus MP, Bakshi VP, Geyer MA. Isolation rearing affects sequential organization of motor behavior in post-pubertal but not pre-pubertal Lister and Sprague-Dawley rats. Behav Brain Res 1998, 94: 271–280.CrossRefGoogle Scholar
  45. 45.
    Geyer MA, Wilkinson LS, Humby T, Robbins TW. Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol Psychiatry 1993, 34: 361–372.CrossRefGoogle Scholar
  46. 46.
    Jones GH, Marsden CA, Robbins TW. Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates. Behav Brain Res 1991, 43: 35–50.CrossRefGoogle Scholar
  47. 47.
    Li N, Ping J, Wu R, Wang C, Wu X, Li L. Auditory fear conditioning modulates prepulse inhibition in socially reared rats and isolation-reared rats. Behav Neurosci 2008, 122: 107–118.CrossRefGoogle Scholar
  48. 48.
    Li N, Wu X, Li L. Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats. Behav Pharmacol 2007, 18: 135–145.CrossRefGoogle Scholar
  49. 49.
    Reboucas RC, Schmidek WR. Handling and isolation in three strains of rats affect open field, exploration, hoarding and predation. Physiol Behav 1997, 62: 1159–1164.CrossRefGoogle Scholar
  50. 50.
    Varty GB, Paulus MP, Braff DL, Geyer MA. Environmental enrichment and isolation rearing in the rat: effects on locomotor behavior and startle response plasticity. Biol Psychiatry 2000, 47: 864–873.CrossRefGoogle Scholar
  51. 51.
    Wilkinson LS, Killcross SS, Humby T, Hall FS, Geyer MA, Robbins TW. Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacology 1994, 10: 61–72.CrossRefGoogle Scholar
  52. 52.
    Day-Wilson KM, Jones DN, Southam E, Cilia J, Totterdell S. Medial prefrontal cortex volume loss in rats with isolation rearing-induced deficits in prepulse inhibition of acoustic startle. Neuroscience 2006, 141: 1113–1121.CrossRefGoogle Scholar
  53. 53.
    Harte MK, Powell SB, Reynolds LM, Swerdlow NR, Geyer MA, Reynolds GP. Reduced N-acetylaspartate in the temporal cortex of rats reared in isolation. Biol Psychiatry 2004, 56: 296–299.CrossRefGoogle Scholar
  54. 54.
    Heidbreder CA, Foxton R, Cilia J, Hughes ZA, Shah AJ, Atkins A, et al. Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation. Psychopharmacology (Berl) 2001, 156: 338–351.CrossRefGoogle Scholar
  55. 55.
    Jones GH. Social isolation and individual differences: behavioural and dopaminergic responses to psychomotor stimulants. Clin Neuropharmacol 1992, 15 Suppl 1 Pt A: 253A–254A.Google Scholar
  56. 56.
    Jones GH, Hernandez TD, Kendall DA, Marsden CA, Robbins TW. Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry. Pharmacol Biochem Behav 1992, 43: 17–35.CrossRefGoogle Scholar
  57. 57.
    Lapiz MD, Fulford A, Muchimapura S, Mason R, Parker T, Marsden CA. Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission. Neurosci Behav Physiol 2003, 33: 13–29.CrossRefGoogle Scholar
  58. 58.
    Muchimapura S, Mason R, Marsden CA. Effect of isolation rearing on pre- and post-synaptic serotonergic function in the rat dorsal hippocampus. Synapse 2003, 47: 209–217.CrossRefGoogle Scholar
  59. 59.
    Preece MA, Dalley JW, Theobald DE, Robbins TW, Reynolds GP. Region specific changes in forebrain 5-hydroxytryptamine1A and 5-hydroxytryptamine2A receptors in isolation-reared rats: an in vitro autoradiography study. Neuroscience 2004, 123: 725–732.CrossRefGoogle Scholar
  60. 60.
    Gilabert-Juan J, Moltó MD, Nacher J. Post-weaning social isolation rearing influences the expression of molecules related to inhibitory neurotransmission and structural plasticity in the amygdala of adult rats. Brain Res 2012, 1448: 129–136.CrossRefGoogle Scholar
  61. 61.
    Quan MN, Tian YT, Xu KH, Zhang T, Yang Z. Post weaning social isolation influences spatial cognition, prefrontal cortical synaptic plasticity and hippocampal potassium ion channels in Wistar rats. Neuroscience 2010, 169: 214–222.CrossRefGoogle Scholar
  62. 62.
    Han X, Wang W, Shao F, Li N. Isolation rearing alters social behaviors and monoamine neurotransmission in the medial prefrontal cortex and nucleus accumbens of adult rats. Brain Res 2011, 1385: 175–181.CrossRefGoogle Scholar
  63. 63.
    Liu Y, Jiang Y, Si Y, Kim JY, Chen ZF, Rao Y. Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature 2011, 472: 95–99.CrossRefGoogle Scholar
  64. 64.
    Zhao ZQ, Scott M, Chiechio S, Wang JS, Renner KJ, Gereau RWt, et al. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J Neurosci 2006, 26: 12781–12788.Google Scholar
  65. 65.
    Seyer B, Pham V, Albiston AL, Chai SY. Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory. Neurosci Lett 2016, 628: 171–178.CrossRefGoogle Scholar
  66. 66.
    Morelli E, Moore H, Rebello TJ, Gray N, Steele K, Esposito E, et al. Chronic 5-HT transporter blockade reduces DA signaling to elicit basal ganglia dysfunction. J Neurosci 2011, 31: 15742–15750.CrossRefGoogle Scholar
  67. 67.
    Brunner D, Buhot MC, Hen R, Hofer M. Anxiety, motor activation, and maternal-infant interactions in 5HT1B knockout mice. Behav Neurosci 1999, 113: 587–601.CrossRefGoogle Scholar
  68. 68.
    Li L, Du Y, Li N, Wu X, Wu Y. Top-down modulation of prepulse inhibition of the startle reflex in humans and rats. Neurosci Biobehav Rev 2009, 33: 1157–1167.CrossRefGoogle Scholar
  69. 69.
    Marsden CA, King MV, Fone KC. Influence of social isolation in the rat on serotonergic function and memory–relevance to models of schizophrenia and the role of 5-HT receptors. Neuropharmacology 2011, 61: 400–407.CrossRefGoogle Scholar
  70. 70.
    van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature 2010, 468: 203–212.CrossRefGoogle Scholar
  71. 71.
    Ibi D, Takuma K, Koike H, Mizoguchi H, Tsuritani K, Kuwahara Y, et al. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. J Neurochem 2008, 105: 921–932.CrossRefGoogle Scholar
  72. 72.
    Settle EC, Jr. Antidepressant drugs: disturbing and potentially dangerous adverse effects. J Clin Psychiatry 1998, 59 Suppl 16: 25–30; discussion 40–22.Google Scholar
  73. 73.
    Cassano P, Fava M. Tolerability issues during long-term treatment with antidepressants. Ann Clin Psychiatry 2004, 16: 15–25.CrossRefGoogle Scholar
  74. 74.
    Damsa C, Bumb A, Bianchi-Demicheli F, Vidailhet P, Sterck R, Andreoli A, et al. “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review. J Clin Psychiatry 2004, 65: 1064–1068.CrossRefGoogle Scholar
  75. 75.
    Preskorn SH. Reboxetine: a norepinephrine selective reuptake pump inhibitor. J Psychiatr Pract 2004, 10: 57–63.CrossRefGoogle Scholar
  76. 76.
    Ago Y, Sakaue M, Baba A, Matsuda T. Selective reduction by isolation rearing of 5-HT1A receptor-mediated dopamine release in vivo in the frontal cortex of mice. J Neurochem 2002, 83: 353–359.CrossRefGoogle Scholar
  77. 77.
    Song N, Xie J. Iron, Dopamine, and alpha-synuclein interactions in at-Risk dopaminergic neurons in Parkinson’s disease. Neurosci Bull 2018, 34: 382–384.CrossRefGoogle Scholar
  78. 78.
    Qian A, Wang X, Liu H, Tao J, Zhou J, Ye Q, et al. Dopamine D4 receptor gene associated with the frontal-striatal-cerebellar loop in children with ADHD: a resting-state fMRI study. Neurosci Bull 2018, 34: 497–506.CrossRefGoogle Scholar
  79. 79.
    Shin JK, Malone DT, Crosby IT, Capuano B. Schizophrenia: a systematic review of the disease state, current therapeutics and their molecular mechanisms of action. Curr Med Chem 2011, 18: 1380–1404.CrossRefGoogle Scholar
  80. 80.
    Hayes DJ, Greenshaw AJ. 5-HT receptors and reward-related behaviour: a review. Neurosci Biobehav Rev 2011, 35: 1419–1449.CrossRefGoogle Scholar
  81. 81.
    Savelieva KV, Zhao S, Pogorelov VM, Rajan I, Yang Q, Cullinan E, et al. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS One 2008, 3: e3301.CrossRefGoogle Scholar
  82. 82.
    Belmaker RH, Agam G, Bersudsky Y. Role of GSK3beta in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A 2008, 105: E23; author reply E24.Google Scholar
  83. 83.
    Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M, et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A 1998, 95: 14476–14481.CrossRefGoogle Scholar
  84. 84.
    Jia YF, Song NN, Mao RR, Li JN, Zhang Q, Huang Y, et al. Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells. Front Behav Neurosci 2014, 8: 325.CrossRefGoogle Scholar
  85. 85.
    Ago Y, Araki R, Tanaka T, Sasaga A, Nishiyama S, Takuma K, et al. Role of social encounter-induced activation of prefrontal serotonergic systems in the abnormal behaviors of isolation-reared mice. Neuropsychopharmacology 2013, 38: 1535–1547.CrossRefGoogle Scholar
  86. 86.
    Mosienko V, Matthes S, Hirth N, Beis D, Flinders M, Bader M, et al. Adaptive changes in serotonin metabolism preserve normal behavior in mice with reduced TPH2 activity. Neuropharmacology 2014, 85: 73–80.CrossRefGoogle Scholar

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

Personalised recommendations