Changes in Monoamine Levels in BALB/c and 57Bl/6N Mice in Response to Acute Stress with Different Controllability

  • K. A. KasabovEmail author
  • D. A. Shakhovtsev
  • N. V. Malyshev
  • M. A. Konstantinov
  • V. B. Narkevich
  • V. S. Kudrin
  • E. A. Anderzhanova

The severity and specificity of CNS disturbances resulting from negative psychoemotional experience are determined by not only genetically determined stress sensitivity, but also epigenetic factors; among the latter, the context of stress exposure, e.g. stress controllability is considered. We examined the effect of controllability factor on behavioral and neurochemical parameters of acute stress in the elevated plus maze test. The situations of controllable and uncontrollable stress were modeled by allowing or restricting mice in their choice for closed arms during testing in the maze. The anxiety level of inbred BALB/c and C57Bl/6N mice was assessed and the levels and monoamine turnover in the medial prefrontal cortex, hippocampus, amygdala, and hypothalamus were measured. It was found that the decrease in stress controllability suppresses explorative activity in mice; the behavioral and neurochemical differences between the two strains are not constant feature and depend on stress controllability; serotoninergic and dopaminerigic neurotransmission in the hypothalamus can be a signal to discriminate stress controllability in the brain.

Key Words

controllability of psychophysiological stress BALB/c C57Bl/6N mice elevated plus maze monoamines 


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  1. 1.
    Anderzhanova EA, Bächli H, Buneeva OA, Narkevich VB, Medvedev AE, Thoeringer CK, Wotjak CT, Kudrin VS. Strain differences in profiles of dopaminergic neurotransmission in the prefrontal cortex of the BALB/C vs. C57Bl/6 mice: consequences of stress and afobazole. Eur. J. Pharmacol. 2013;708(1-3):95-104.CrossRefGoogle Scholar
  2. 2.
    Bondar’ NP, Kovalenko IL, Avgustinovich DF, Kudriavtseva NN. Influence of experimental context on the development of anhedonia in male mice exposed to chronic social stress. Zh. Vyssh. Nerv. Deiat. Im. I.P. Pavlova. 2008;58(2):238-246.PubMedGoogle Scholar
  3. 3.
    File SE. The interplay of learning and anxiety in the elevated plus-maze. Behav. Brain Res. 1993;58(1-2):199-202.CrossRefGoogle Scholar
  4. 4.
    Gudsnuk K, Champagne FA. Epigenetic influence of stress and the social environment. ILAR J. 2012;53(3-4):279-288.CrossRefGoogle Scholar
  5. 5.
    Harro J. Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and why. Behav. Brain Res. 2018;352:81-93.CrossRefGoogle Scholar
  6. 6.
    Heinz DE, Genewsky A, Wotjak CT. Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle. Neuropharmacology. 2017;126:233-241.CrossRefGoogle Scholar
  7. 7.
    Kao CY, Stalla G, Stalla J, Wotjak CT, Anderzhanova E. Norepinephrine and corticosterone in the medial prefrontal cortex and hippocampus predict PTSD-like symptoms in mice. Eur. J. Neurosci. 2015;41(9):1139-1148.CrossRefGoogle Scholar
  8. 8.
    Kudrin VS, Klodt PM, Narkevich VB, Shipilov VA, Poseva VI, Molodavkin GM, Voronina TA. Behavioral and neurochemical aspects of the antidepressive action of GSB-106 dipeptide BDNF fragment. Eksp. Klein. Farmakol. 2012;75(10):3-7.Google Scholar
  9. 9.
    Kulikov AV, Osipova DV, Naumenko VS, Popova NK. Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains. Genes Brain Behav. 2005;4(8):482-485.CrossRefGoogle Scholar
  10. 10.
    Lalonde R, Strazielle C. Relations between open-field, elevated plus- maze, and emergence tests as displayed by C57/BL6J and BALB/c mice. J. Neurosci. Methods. 2008;171(1):48-52.CrossRefGoogle Scholar
  11. 11.
    Liu X, Tang X, Sanford L.D. Stressor controllability and Fos expression in stress regulatory regions in mice. Physiol. Behav. 2009;97(3-4):321-326.CrossRefGoogle Scholar
  12. 12.
    Prince CR, Anisman H. Situation specific effects of stressor controllability on plasma corticosterone changes in mice. Pharmacol. Biochem. Behav. 1990;37(4):613-621.CrossRefGoogle Scholar
  13. 13.
    Roth TL. Epigenetic mechanisms in the development of behavior: advances, challenges, and future promises of a new field. Develop. Psychopathol. 2013;25(4, Pt 2):127911291.Google Scholar
  14. 14.
    Seredenin SB, Lapitskaya AS, Nadorov SA, Kudrin VS, Badyshtov BA. Multidimensional assessment of differences in monoamine metabolism in C57BL/6 and BALB/c mice. Bull. Exp. Biol. Med. 2000;129(5):487-490.CrossRefGoogle Scholar
  15. 15.
    Wellman LL, Yang L, Sanford LD. Effects of corticotropin releasing factor (CRF) on sleep and temperature following predictable controllable and uncontrollable stress in mice. Front. Neurosci. 2015;9. ID 258. doi:

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • K. A. Kasabov
    • 1
    Email author
  • D. A. Shakhovtsev
    • 2
  • N. V. Malyshev
    • 2
  • M. A. Konstantinov
    • 2
  • V. B. Narkevich
    • 1
  • V. S. Kudrin
    • 1
  • E. A. Anderzhanova
    • 1
    • 3
  1. 1.V. V. Zakusov Research Institute of PharmacologyMoscowRussia
  2. 2.N. I. Pirogov Russian National Research Medical UniversityMinistry of Health of Russian FederationMoscowRussia
  3. 3.University Hospital Bonn, Clinic of Psychiatry and PsychotherapyBonnGermany

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