Neuroscience and Behavioral Physiology

, Volume 44, Issue 3, pp 339–347 | Cite as

Effects of Buspirone on Behavior in Female Mice in a Social Discomfort Model


We report here studies of the effects of single and chronic (14 days) administration of buspirone (1 mg/kg, i.p.) on the behavior of female C57BL/6J mice in conditions of social discomfort induced by prolonged periods of time in a cage with an aggressive male on the other side of a perforated partition and the presence at daily intermale confrontations. These experiments showed that in conditions of social discomfort, female mice showed dynamic changes in the sensitivity of brain 5-HT1A receptors, assessed in terms of the animals’ behavior 30 min after single doses of buspirone. Sensitivity was found to increase at the initial stages of formation of pathological behavior (10 days) and to decrease at 20–30 days. Females with decreased 5-HT1A receptor sensitivity due to 30 days of living in conditions of social discomfort also demonstrated decreased sensitivity to chronic administration of buspirone.


buspirone female C57BL/6J mice social discomfort behavior 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. F. Avgustinovich, “Female anxiety evoked by prolonged psychoemotional conditions,” Ros. Fiziol. Zh., 9, No. 7, 858–867 (2003).Google Scholar
  2. 2.
    D. F. Avgustinovich, G. B. Vishnivetskaya, and L. A. Koryakina, “Effects of acute and chronic administration of buspirone on communicativeness in mice with experience of social defeats,” Byull. Eksperim. Biol. Med., 149, No. 1, 64–68 (2010).Google Scholar
  3. 3.
    D. F. Avgustinovich and I. L. Kovalenko, “Formation of behavioral pathology in female C57BL/6J mice in conditions of prolonged psychoemotional exposure,” Ros. Fiziol. Zh., 90, No. 11, 1324–1336 (2004).Google Scholar
  4. 4.
    E. Akimova, R. Lanzenberger, and S. Kasper, “The serotonin-1A receptor in anxiety disorders,” Biol. Psychiatry, 66, No. 7, 627–635 (2009).PubMedCrossRefGoogle Scholar
  5. 5.
    P. R. Albert and B. L. François, “Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy,” Front. Neurosci., 4, No. 35, 1–7, (2010).Google Scholar
  6. 6.
    B. J. C. Allmann, A. Domantay, and H. S. Schoeman, “Antidepressant activity of buspirone in anxiety,” Curr. Ther. Res., 52, No. 3, 406–411 (1992).CrossRefGoogle Scholar
  7. 7.
    J. T. Apter and L. A. Allen, “Buspirone: future directions,” J. Clin. Psychopharmacol., 19, No. 1, 86–93 (1999).PubMedCrossRefGoogle Scholar
  8. 8.
    F. R. Bambico, N. T. Nguyen, and G. Gobbi, “Decline in serotonergic firing activity and desensitization of 5-HT1A autoreceptors after chronic unpredictable stress,” Eur. Neuropsychopharmacol., 19, No. 3, 215–228 (2009).PubMedCrossRefGoogle Scholar
  9. 9.
    F. Batool, “Buspirone and anxiety disorders: a review with pharmacological and clinical perspectives,” Internet J. Pharmacol. ISSN, 5, No. 2 (2008).Google Scholar
  10. 10.
    V. Birzniece, I. M. Johansson, M. D. Wang, et al., “Serotonin 5-HT(1A) receptor mRNA expression in dorsal hippocampus and raphe nuclei after gonadal hormone manipulation in female rats,” Neuroendocrinology, 74, No. 2, 135–142 (2001).PubMedCrossRefGoogle Scholar
  11. 11.
    P. Blier, R. Bergeron, and C. De Montigny, “Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response,” Neuropsychopharmacology, 16, No. 5, 333–338 (1997).PubMedCrossRefGoogle Scholar
  12. 12.
    P. Blier and N. M. Ward, “Is there a role for 5-HT1A agonists in the treatment of depression?” Biol. Psychiatry, 53, No. 3, 193–203 (2003).PubMedCrossRefGoogle Scholar
  13. 13.
    C. Saccia, I. Conti, G. Viganò, and S. Garattini, “1-(2-Pyridinyl)-piperazine as active metabolite of buspirone in man and rat,” Pharmacology, 33, No. 1, 46–51 (1986).CrossRefGoogle Scholar
  14. 14.
    L. Cervo, G. Grignaschi, and R. Samanin, “Different effects of intracerebral and systemic administration of buspirone in the forced swimming test: involvement of a metabolite,” Life Sci., 43, No. 25, 2095–2102 (1988).PubMedCrossRefGoogle Scholar
  15. 15.
    J. F. Cryan, A. Markou, and I. Lucki, “Assessing antidepressant activity in rodents: recent developments and future needs,” Trends Pharmacol. Sci., 23, No. 5, 238–245 (2002).PubMedCrossRefGoogle Scholar
  16. 16.
    J. G. Hensler, “Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration,” Life Sci., 72, No. 15, 1665–1682 (2003).PubMedCrossRefGoogle Scholar
  17. 17.
    B. J. Jones and T. P. Blackburn, “The medical benefit of 5-HT research,” Pharmacol. Biochem. Behav., 71, No. 4, 555–568 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    N. Kieran, X. M. Ou, and A. H. Iyo, “Chronic social defeat down regulates the 5-HT1A receptor but not Freud-1 of NUDR in the rat prefrontal cortex,” Neurosci. Lett., 469, No. 3, 380–384 (2010).PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    N. N. Kudryavtseva “Experience of defeats decreases the behavioral reactivity to conspecific in partition test,” Behav. Process, 32, 297–304 (1994).CrossRefGoogle Scholar
  20. 20.
    N. Laaris, E. Le Poul, A. M. Laporte, et al., “Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study,” Neuroscience, 91, No. 3, 947–958 (1999).PubMedCrossRefGoogle Scholar
  21. 21.
    L. Lanfumey and M. Hamon, “Central 5-HT(1A) receptors: regional distribution and functional characteristics,” Nucl. Med. Biol., 27, No. 5, 429–435 (2000).PubMedCrossRefGoogle Scholar
  22. 22.
    L. Lanfumey and M. Hamon, “5-HT1 receptors,” Curr. Drug Targets CNS Neurol. Disord., 3, No. 1, 1–10 (2004).PubMedCrossRefGoogle Scholar
  23. 23.
    L. Lanfumey, M. C. Pardon, N. Laaris, et al., “5-HT1A autoreceptor desensitization by chronic ultramild stress in mice,” Neuroreport, 10, No. 16, 3369–3374 (1999).PubMedCrossRefGoogle Scholar
  24. 24.
    R. R. Lanzenberger, M. Mitterhauser, C. Spindelegger, et al., “Reduced serotonin-1A receptor binding in social anxiety disorder,” Biol. Psychiatry, 61, No. 9, 1081–1089 (2007).PubMedCrossRefGoogle Scholar
  25. 25.
    K. P. Lesch, Y. Zeng, A. Reif, and L. Gutknecht, “Anxiety-related traits in mice with modified genes of the serotonergic pathway,” Eur. J. Pharmacol., 480, No. 1–3, 185–204 (2003).PubMedCrossRefGoogle Scholar
  26. 26.
    J. Levine, D. P. Cole, K. N. Chengappa, and S. Gershon, “Anxiety disorders and major depression, together or apart,” Depress. Anxiety, 14, No. 2, 94–104 (2001).PubMedCrossRefGoogle Scholar
  27. 27.
    Q. Li, “Cellular and molecular alterations in animal models of serotonin transporter disruption: a comparison between developmental and adult stages,” in: Experimental Models in Serotonin Transporter Research, A. V. Kalueff and J. L. LaPorte (eds.), Cambridge University Press, Cambridge (2010), pp. 43–77.Google Scholar
  28. 28.
    Y. P. Liu, L. S. Wilkinson, and T. W. Robbins, “Effects of acute and chronic buspirone on impulsive choice and efflux of 5-HT and dopamine in hippocampus, nucleus accumbens and prefrontal cortex,” Psychopharmacology (Berlin), 173, No. 1–2, 175–185 (2004).CrossRefGoogle Scholar
  29. 29.
    N. Z. Lu and C. L. Bethea, “Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys,” Neuropsychopharmacology, 27, 12–24 (2002).PubMedCrossRefGoogle Scholar
  30. 30.
    B. B. Lydiard, and O. Brawman-Mintzer, “Anxious depression,” J. Clin. Psychiatry, 59, Supplement 18, 10–17 (1998).Google Scholar
  31. 31.
    E. Majercsik, J. Haller, C. Leveleki, et al., “The effect of social factors on the anxiolytic efficacy of buspirone in male rats, male mice, and men,” Prog. Neuropsychol. Biol. Psychiatry, 27, No. 8, 1187–1199 (2003).CrossRefGoogle Scholar
  32. 32.
    M. J. Millan, “The neurobiology and control of anxious state,” Prog. Neurobiol., 70, 83–244 (2003).PubMedCrossRefGoogle Scholar
  33. 33.
    P. C. Moser, “An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone,” Psychopharmacology (Berlin), 99, No. 1, 48–53 (1989).CrossRefGoogle Scholar
  34. 34.
    C. B. Nemeroff, “Anxiolytics: past, present, and future agents,” J. Clin. Psychiatry, 64, Suppl. 3, 3–6 (2003).PubMedGoogle Scholar
  35. 35.
    P. T. Ninan and S. Muntasser, “Buspirone,” in: Essentials of Clinical Psychopharmacology, A. F. Schatzberg and C. B. Nemeroff (eds.), Am. Psychiatric Publ. Inc., Washington DC, London (2006), pp. 199–207.Google Scholar
  36. 36.
    K. Nishi, K. Kanemaru, S. Hasegawa, et al., “Both acute and chronic buspirone treatment have different effects on regional 5-HT synthesis in Flinders Sensitive Line rats (a rat model of depression) than in control rats,” Neurochem. Int., 54, No. 3–4, 205–214 (2009).PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    A. M. Novick, “Antidepressant psychopharmacology and social brain,” Psychiatry, 74, No. 1, 72–86 (2011).PubMedGoogle Scholar
  38. 38.
    M. H. Pollack, “Refractory generalized anxiety disorder,” J. Clin. Psychiatry, 70, Supplement 2, 32–38 (2009).Google Scholar
  39. 39.
    L. Prut and C. Belzung, “The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review,” Eur. J. Pharmacol., 463, No. 1–3, 3–33 (2003).PubMedCrossRefGoogle Scholar
  40. 40.
    S. Ramboz, R. Oosting, D. A. Amara, et al., “Serotonin receptor 1A knockout: An animal model of anxiety-related disorder,” Proc. Natl. Acad. Sci. USA, 95, No. 24, 14476–14781 (1998).PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    K. W. Rickels, K. Weisman, N. Norstad, et al., “Buspirone and diazepam in anxiety: a controlled study,” J. Clin. Psychiatry, 43, No. 12, Part 2, 81–86 (1982).Google Scholar
  42. 42.
    H. Sato, I. Skelin, G. Debonnel, and M. Diksic, “Chronic buspirone treatment normalizes open field behavior in olfactory bulbectomized rats: assessment with a quantitative autoradiographic evaluation of the 5-HT1A binding sites,” Brain Res. Bull., 75, No. 5, 545–555 (2008).PubMedCrossRefGoogle Scholar
  43. 43.
    J. Savitz, I. Lucki, and W. C. Drevets, “5-HT(1A) receptor function in major depressive disorder,” Prog. Neurobiol., 88, No. 1, 17–31 (2009).PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    L. J. Sim-Selley, L. J. Vogt, R. Xiao, et al., “Region-specific changes in 5-HT(1A) receptor-activated G-proteins in rat brain following chronic buspirone,” Eur. J. Pharmacol., 389, No. 2–3, (2000).Google Scholar
  45. 45.
    S. M. Stahl, “Mixed depression and anxiety: serotonin1A receptors as a common pharmacologic link,” J. Clin. Psychiatry, 58, Suppl. 8, 20–26 (1997).PubMedGoogle Scholar
  46. 46.
    J. Tauscher, R. M. Bagby, M. Javanmard, et al., “Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: A [11C]Way-100635 PET investigation in healthy volunteers,” Am. J. Psychiatry, 158, 1326–1328 (2001).PubMedCrossRefGoogle Scholar
  47. 47.
    M. Toth, “5-HT1A receptor knockout mouse as a genetic model of anxiety,” Eur. J. Pharmacol., 463, 177–184 (2003).PubMedCrossRefGoogle Scholar
  48. 48.
    M. H. Trivedi, M. Fava, S. R. Wisniewski, et al., “STAR*D Study team. Medication augmentation after the failure of SSRIs for depression,” New Eng. J. Med., 354, No. 12, 1243–1252 (2006).PubMedCrossRefGoogle Scholar
  49. 49.
    Wang Shao-hua, Zhang Zhi-jun, Guo Yi-jing, et al., “Decreased expression of serotonin 1A receptor in the dentate gyrus in association with chronic mild stress: A rat model of post-stroke depression,” Psychiatry Res., 170, 245–251 (2009).Google Scholar
  50. 50.
    A. Watanabe, S. Hasegawa, K. Nishi, et al., “Chronic buspirone treatment normalizes regional serotonin synthesis in the olfactory bulbectomized rat brain: an autoradiographic study,” Brain Res. Bull., 69, No. 2, 101–108 (2006).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Cytology and Genetics, Siberian Branch, Russian Academy of SciencesNovosibirskRussia

Personalised recommendations