Skip to main content
SpringerLink
Log in

Nitric Oxide and Serotonin Interactions in Aggression

  • Chapter
  • First Online:
Book cover Neuroscience of Aggression

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 17))

Abstract

Violence is a significant public health problem worldwide. Neurobiological research on violence and aggression attempts to elucidate the cellular and molecular pathways that increase the propensity toward this behavior. Research over the past 40 years has implicated several brain regions and neurotransmitters in aggression, mainly using rodent models. Perhaps the strongest association is the link between serotonin and aggression, which has compelling interactions with the nitric oxide system. Recently, new insights into these relationships have been added as modern techniques allow more sophisticated analyses. This chapter will discuss current developments implicating serotonin and nitric oxide in aggressive behavior. Recently developed high-resolution methods for examining the neurobiological basis of aggression will be considered, with emphasis on future directions for the field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anderson DJ (2012) Optogenetics, sex, and violence in the brain: implications for psychiatry. Biol Psychiatry 71:1081–1089

    Article  PubMed Central  PubMed  Google Scholar 

  • Angoa-Perez M, Kane MJ, Briggs DI, Sykes CE, Shah MM, Francescutti DM et al (2012) Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. J Neurochem 121:974–984

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bedrosian TA, Fonken LK, Demas GE, Nelson RJ (2012) Photoperiod-dependent effects of neuronal nitric oxide synthase inhibition on aggression in Siberian hamsters. Horm Behav 61:176–180

    Google Scholar 

  • Bortolato M, Godar SC, Melis M, Soggiu A, Roncada P, Casu A et al (2012) NMDARs mediate the role of monoamine oxidase A in pathological aggression. J Neurosci 32:8574–8582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Breuillaud L, Rossetti C, Meylan EM, Merinat C, Halfon O, Magistretti PJ et al (2012) Deletion of CREB-regulated transcription coactivator 1 induces pathological aggression, depression-related behaviors, and neuroplasticity genes dysregulation in mice. Biol Psychiatry 72:528–536

    Article  CAS  PubMed  Google Scholar 

  • Chiavegatto S, Dawson VL, Mamounas LA, Koliatsos VE, Dawson TM, Nelson RJ (2001) Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase. Proc Natl Acad Sci U S A 98:1277–1281

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Clinton SM, Kerman IA, Orr HR, Bedrosian TA, Abraham AD, Simpson DN et al (2011) Pattern of forebrain activation in high novelty-seeking rats following aggressive encounter. Brain Res 1422:20–31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Coccaro EF, Lee R, Liu T, Mathe AA (2012) Cerebrospinal fluid neuropeptide Y-like immunoreactivity correlates with impulsive aggression in human subjects. Biol Psychiatry 72(12):997–1003

    Google Scholar 

  • Demas GE, Eliasson MJ, Dawson TM, Dawson VL, Kriegsfeld LJ, Nelson RJ et al (1997) Inhibition of neuronal nitric oxide synthase increases aggressive behavior in mice. Mol Med 3:610–616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fish EW, Faccidomo S, Miczek KA (1999) Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253. Psychopharmacology 146:391–399

    Article  CAS  PubMed  Google Scholar 

  • Gammie SC, Nelson RJ (1999) Maternal aggression is reduced in neuronal nitric oxide synthase-deficient mice. J Neurosci 19:8027–8035

    CAS  PubMed  Google Scholar 

  • Garattini S, Giacalone E, Valzelli L (1967) Isolation, aggressiveness and brain 5-hydroxytryptamine turnover. J Pharm Pharmacol 19:338–339

    Article  CAS  PubMed  Google Scholar 

  • Giacalone E, Tansella M, Valzelli L, Garattini S (1968) Brain serotonin metabolism in isolated aggressive mice. Biochem Pharmacol 17:1315–1327

    Article  CAS  PubMed  Google Scholar 

  • Hoyer SC, Eckart A, Herrel A, Zars T, Fischer SA, Hardie SL et al (2008) Octopamine in male aggression of Drosophila. Curr Biol 18:159–167

    Article  CAS  PubMed  Google Scholar 

  • Jensen KP, Covault J, Conner TS, Tennen H, Kranzler HR, Furneaux HM (2009) A common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors. Mol Psychiatry 14:381–389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Karl T, Lin S, Schwarzer C, Sainsbury A, Couzens M, Wittmann W et al (2004) Y1 receptors regulate aggressive behavior by modulating serotonin pathways. Proc Natl Acad Sci U S A 101:12742–12747

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kerman IA, Clinton SM, Bedrosian TA, Abraham AD, Rosenthal DT, Akil H et al (2011) High novelty-seeking predicts aggression and gene expression differences within defined serotonergic cell groups. Brain Res 1419:34–45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kravitz EA, Huber R (2003) Aggression in invertebrates. Curr Opin Neurobiol 13:736–743

    Article  CAS  PubMed  Google Scholar 

  • Kriegsfeld LJ, Dawson TM, Dawson VL, Nelson RJ, Snyder SH (1997) Aggressive behavior in male mice lacking the gene for neuronal nitric oxide synthase requires testosterone. Brain Res 769:66–70

    Article  CAS  PubMed  Google Scholar 

  • Laas K, Reif A, Herterich S, Eensoo D, Lesch KP, Harro J (2010) The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity. Psychopharmacology 209:255–261

    Article  CAS  PubMed  Google Scholar 

  • Lesch KP, Merschdorf U (2000) Impulsivity, aggression, and serotonin: a molecular psychobiological perspective. Behav Sci Law 18:581–604

    Article  CAS  PubMed  Google Scholar 

  • Lin D, Boyle MP, Dollar P, Lee H, Lein ES, Perona P et al (2011) Functional identification of an aggression locus in the mouse hypothalamus. Nature 470:221–226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH et al (1999) Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci U S A 96:15239–15244

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maas JW (1962) Neurochemical differences between two strains of mice. Science 137:621–622

    Article  CAS  PubMed  Google Scholar 

  • Miczek KA, Hussain S, Faccidomo S (1998) Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists. Psychopharmacology 139:160–168

    Article  CAS  PubMed  Google Scholar 

  • Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM et al (1995) Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 378:383–386

    Article  CAS  PubMed  Google Scholar 

  • Olivier B, Mos J, van Oorschot R, Hen R (1995) Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry 28(Suppl 2):80–90

    Article  PubMed  Google Scholar 

  • Reif A, Jacob CP, Rujescu D, Herterich S, Lang S, Gutknecht L et al (2009) Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Arch Gen Psychiatry 66:41–50

    Article  CAS  PubMed  Google Scholar 

  • Reif A, Kiive E, Kurrikoff T, Paaver M, Herterich S, Konstabel K, et al (2010) A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity. Psychopharmacology 44(3):222–238

    Google Scholar 

  • Ribeiro AC, Musatov S, Shteyler A, Simanduyev S, Arrieta-Cruz I, Ogawa S et al (2012) siRNA silencing of estrogen receptor-alpha expression specifically in medial preoptic area neurons abolishes maternal care in female mice. Proc Natl Acad Sci U S A 109:16324–16329

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L et al (1994) Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265:1875–1878

    Article  CAS  PubMed  Google Scholar 

  • Simon NG, Lu SF (2005) Androgens and aggression. In: Nelson RJ (ed) Biology of aggression. Oxford University Press, New York

    Google Scholar 

  • Takahashi A, Shimamoto A, Boyson CO, DeBold JF, Miczek KA (2010) GABA(B) receptor modulation of serotonin neurons in the dorsal raphe nucleus and escalation of aggression in mice. J Neurosci 30:11771–11780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Trainor BC, Workman JL, Jessen R, Nelson RJ (2007) Impaired nitric oxide synthase signaling dissociates social investigation and aggression. Behav Neurosci 121:362–369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang D, Szyf M, Benkelfat C, Provencal N, Turecki G, Caramaschi D et al (2012) Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression. PLoS ONE 7:e39501

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wen JC, Hotchkiss AK, Demas GE, Nelson RJ (2004) Photoperiod affects neuronal nitric oxide synthase and aggressive behaviour in male Siberian hamsters (Phodopus sungorus). J Neuroendocrinol 16:916–921

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, The Ohio State University Wexner Medical Center, 636 Biomedical Research Tower, 460 W. 12th Avenue, Columbus, OH, 43210, USA

    Tracy A. Bedrosian

  2. Department of Neuroscience, The Ohio State University Wexner Medical Center, 4084 Graves Hall, 333 W. 10th Avenue, Columbus, OH, 43210, USA

    Randy J. Nelson

Authors
  1. Tracy A. Bedrosian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Randy J. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tracy A. Bedrosian .

Editor information

Editors and Affiliations

  1. Moses Hunt Professor of Psychology, Psychiatry, Pharmacol & Neurosci, Tufts University, Medford, Massachusetts, USA

    Klaus A. Miczek

  2. Dept of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

    Andreas Meyer-Lindenberg

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bedrosian, T.A., Nelson, R.J. (2013). Nitric Oxide and Serotonin Interactions in Aggression. In: Miczek, K., Meyer-Lindenberg, A. (eds) Neuroscience of Aggression. Current Topics in Behavioral Neurosciences, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2013_273

Download citation

Publish with us

Policies and ethics

Search

Navigation