Neuroscience and Behavioral Physiology

, Volume 37, Issue 6, pp 631–635 | Cite as

Involvement of brain serotonin 5-HT1A receptors in genetic predisposition to aggressive behavior

  • N. K. Popova
  • V. S. Naumenko
  • I. Z. Plyusnina


Experiments were performed on Norwegian rats selected over more than 59 generations for high and low levels of high-affective defensive aggressivity and on highly aggressive (offensive) Tg8 mice with irreversible monoamine oxidase A knockout. There were significant differences in the functional state and expression of 5-HT1A receptors between highly aggressive and non-aggressive animals. Functional activity assessed in terms of hypothermia evoked by a 5-HT1A agonist was significantly greater in non-aggressive rats and mice than in aggressive animals. The high level of functional activity in non-aggressive rats coincided with a greater level of expression of 5-HT1A receptors in the midbrain. The level of 5-HT1A receptor mRNA in aggressive mice was unchanged in the midbrain and hypothalamus and was increased in the frontal cortex and amygdaloid complex. These results led to the conclusion that 5-HT1A receptors play a significant role in the mechanisms of genetic predisposition to aggressive behavior.

Key words

aggressive behavior serotonin 5-HT1A receptors 5-HT1A receptor mRNA 8-OH-DPAT hypothermia MAO A knockout mice rats 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G. B. Vishnivetskaya, I. Z. Plyusnina, and N. K. Popova, “Involvement of 5-HT1A receptors in the control of various types of aggressive behavior,” Zh. Vyssh. Nerv. Deyat., 51, No. 6, 715–719 (2001).Google Scholar
  2. 2.
    A. V. Kulikov, D. V. Osipova, V. S. Naumenko, and N. K. Popova, “The C1473G polymorphism in the tryptophan hydroxylase gene and the extent of aggressive behavior in mice,” Dokl. Ros. Akad. Nauk., 402, No. 4, 571–573 (2005).Google Scholar
  3. 3.
    V. S. Naumenko and A. V. Kulikov, “Quantitative estimation of the expression of the 5-HT1A serotonin receptor gene in the brain,” Mol. Bol., 40, 37–44 (2006).CrossRefGoogle Scholar
  4. 4.
    N. K. Popova, N. N. Voitenko, and L. N. Trut, “Changes in serotonin and 5-Hydroxyindoleacetic acid levels in the brain in silver foxes selected according to behavior,” Dokl. Akad. Nauk. SSSR, 223, No. 6, 1498–1500 (1975).PubMedGoogle Scholar
  5. 5.
    N. K. Popova, Yu. A. Skrinskaya, T. G. Amstislavskaya, G. B. Vishnivetskaya, E. A. Ivanova, I. Seif, and E. De Maier, “Characteristics of the behavior of mice with genetic knockout of the monoamine oxidase type A gene,” Zh. Vyssh. Nerv. Deyat., 50, No. 6, 991–998 (2000).Google Scholar
  6. 6.
    R. Bell and H. Hobson, “5-HT1A receptor influences on rodent social and agonistic behavior,” Neurosci. Biobehav. Rev., 18, 325–338 (1994).PubMedCrossRefGoogle Scholar
  7. 7.
    O. Cases, I. Seif, J. Grimsby, P. Gaspar, K. Chen, S. Pournin, U. Muller, M. Aguet, C. Babinet, J. C. Shih, and E. De Maeyer, “Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAO A,” Science, 268, 1763–1766 (1995).PubMedCrossRefGoogle Scholar
  8. 8.
    A. J. Cleare and A. J. Bond, “Ipsapirone challenge in aggressive men shows an inverse correlation between 5-HT1A receptor function and aggression,” Psychopharmacology, 148, 344–349 (2000).PubMedCrossRefGoogle Scholar
  9. 9.
    S. F. De Boer, M. Lesourd, E. Mocaer, and J. M. Koolhaas, “Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine 1A receptors: a comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, elthoprazine, and WAY-100635,” J. Pharmacol. Exptl. Ther., 288, 1125–1133 (1999).Google Scholar
  10. 10.
    C. T. Dourish, “Brain 5-HT1A receptors and anxiety,” in: Brain 5-HT 1A receptors. Behavioral and Neurochemical Pharmacology, C. T. Dourish, S. Ahlenius, and P. H. Hutson (Eds.), VCH, Ellis Horwood, London (1987), pp. 261–277.Google Scholar
  11. 11.
    A. Evrard, I. Malagie, A. M. Laporte, C. Boni, N. Hanoun, A. C. Trillat, I. Seif, E. De Maeyer, A. Gardier, M. Hamon, and J. Adrien, “Altered regulation of the 5-HT system in the brain of MAO-A knock-out mice,” Eur. J. Neurosci., 15, 841–851 (2002).PubMedCrossRefGoogle Scholar
  12. 12.
    A. V. Kulikov, V. S. Naumenko, I. P. Voronova, M. A. Tikhonova, and N. K. Popova, “Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an external standard,” J. Neurosci. Meth., 141, 92–101 (2005).Google Scholar
  13. 13.
    A. V. Kulikov, D. V. Osipova, V. S. Naumenko, and N. K. Popova, “Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains,” Genes Brain Behav., 4, 482–485 (2005).PubMedCrossRefGoogle Scholar
  14. 14.
    I. Lucki, A. Singh, and D. S. Kreiss, “Antidepressant-like behavioral effects of serotonin receptor agonists,” Neurosci. Biobehav. Rev., 18, 85–95 (1994).PubMedCrossRefGoogle Scholar
  15. 15.
    A. C. Maxson, “Aggression: concepts and methods relevant to genetic analyses in mice and humans, ” in: Neurobehavioral Genetics. Methods and Applications, B. C. Jones and P. Mormede (Eds.), CRC Press LLC, Boca Raton, Florida, New York (2000), pp. 293–300.Google Scholar
  16. 16.
    K. A. Miczek, S. Hussain, and S. Faccidomo, “Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists,” Psychopharmacology, 139, 160–168 (1998).PubMedCrossRefGoogle Scholar
  17. 17.
    E. V. Naumeko, N. K. Popova, E. M. Nikulina, N. N. Dygalo, G. T. Shishkina, P. M. Borodin, and A. L. Markel, “Behavior, adrenocortical activity, and brain monoamines in Norway rats selected for reduced aggressiveness towards man,” Pharmacol. Biochem. Behav., 33, 85–91 (1989).CrossRefGoogle Scholar
  18. 18.
    B. Olivier, J. Mos, R. van Oorshot, and R. Hen, “Serotonin receptors and animal model of aggressive behavior,” Pharmacopsychiatry, 28, 80–90 (1995).PubMedCrossRefGoogle Scholar
  19. 19.
    G. Pineyro and P. Blier, “Autoregulation of serotonin neurons: role in antidepressant drug action,” Pharmacol. Rev., 51, 533–591 (1999).PubMedGoogle Scholar
  20. 20.
    I. Plyusnina and I. Oskina, “Behavioral and adrenocortical responses to open-field test in rats selected for reduced aggressiveness towards humans,” Physiol. Behav., 61, 381–385 (1997).PubMedCrossRefGoogle Scholar
  21. 21.
    N. K. Popova, D. F. Avgustinovich V. G. Kolpakov, and I. Z. Plyusnina, “Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed to various defense behavior strategies,” Pharmacol. Biochem. Behav., 59, 793–797 (1998).PubMedCrossRefGoogle Scholar
  22. 22.
    N. Popova, M. Gilinsky, T. Amstislavskaya, E. Morosova, T. Seif, and E. De Maeyer, “Regional serotonin metabolism in the brain of transgenic mice lacking monoamine oxidase A,” J. Neurosci. Res., 66, 423–427 (2001).PubMedCrossRefGoogle Scholar
  23. 23.
    N. K. Popova, A. V. Kulikov, E. M. Nikulina, E. Yu. Kozlachkova, and G. B. Maslova, “Serotonin metabolism and serotonergic receptors in Norway rats selected for low aggressiveness to man,” Aggress. Behav., 17, 207–213 (1991).CrossRefGoogle Scholar
  24. 24.
    N. K. Popova, G. B. Vishnivetskaya, E. A. Ivanova, J. A. Skrinskaya, and I. Seif, “Altered behavior and alcohol tolerance in transgenic mice lacking MAO A: a comparison with effects of MAO A inhibitor clorgyline,” Pharmacol. Biochem. Behav., 67, 719–727 (2000).PubMedCrossRefGoogle Scholar
  25. 25.
    N. K. Popova, N. N. Voitenko, A. V. Kulikov, and D. F. Avgustinovich, “Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes,” Pharmacol. Biochem. Behav., 40, 751–756 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    S. N. Pradhan, “Aggression and central neurotransmitters,” Int. Rev. Neurobiol., 18, 213–262 (1975).PubMedCrossRefGoogle Scholar
  27. 27.
    K. Pruus, T. Skrebuhhova-Malmros, R. Rudissaar, V. Matto, and L. Allikmets, “5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behavior in adult male Wistar rats,” J. Physiol. Pharmacol., 51, 833–846 (2002).Google Scholar
  28. 28.
    F. Saudou and R. Hen, “5-Hydroxytryptamine receptor subtypes: Molecular and functional diversity,” Adv. Pharmacol., 30, 327–380 (1994).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • N. K. Popova
    • 1
  • V. S. Naumenko
    • 1
  • I. Z. Plyusnina
    • 1
  1. 1.Behavioral Neurogenetics Laboratory, Institute of Cytology and Genetics, Siberian DivisionRussian Academy of SciencesNovosibirsk

Personalised recommendations