Neurochemical Journal

, Volume 10, Issue 2, pp 115–119 | Cite as

The stress effects of a single injection of isotonic saline solution: systemic (blood) and central (frontal cortex and dorsal and ventral hippocampus)

  • S. V. Freiman
  • M. V. OnufrievEmail author
  • M. Yu. Stepanichev
  • Yu. V. Moiseeva
  • N. A. Lazareva
  • N. V. Gulyaeva
Experimental Articles


In experiments with animals, a group that is injected with the vehicle in which a drug of interest is dißsolved is often used as a control. However, even a single injection of a vehicle is a stressor, i.e., “treatment stress,” which may significantly affect some stress-sensitive indices. In the present study, we report some data on the effects of a single intraperitoneal injection of isotonic saline solution on the contents of corticosterone, nitric oxide metabolites, and oxidative capacity, as well as on the expression of proteins and mRNAs of proinflammatory cytokines in the blood and brain regions of rats within one day after the injection as compared to intact animals. At the early time points after the injection, corticosterone contents were substantially elevated in the blood and ventral hippocampus. The content of nitric oxide metabolites decreased in the blood and remained stably low within 2–24 h after the injection. The injection did not affect the contents of proinflammatory cytokines in the blood; however, early after the injection the expression of IL-1ß mRNA decreased in the ventral hippocampus and frontal cortex, whereas 24 h after this treatment, the expression of TNF-a mRNA increased by a factor of 4 in the frontal cortex. Thus, a single injection of isotonic saline solution had a clear stress-producing effect, which was observed at the systemic level and in stress-sensitive brain regions. The strength of this stressful event was sufficient to activate the hypothalamus–pituitary–adrenal axis but not sufficient to induce a significant inflammatory response. The frontal cortex was most sensitive to this treatment; the alterations in the ventral hippocampus were less expressed, whereas the dorsal hippocampus was most stress resistant. Our data show that it is important to consider and thoroughly analyze the effects of “treatment stress” in experiments using injections of biologically active substances.


stress corticosterone proinflammatory cytokines nitric oxide metabolites oxidative capacity 



ventral hippocampus


hypothalamus- pituitary-adrenal axis


dorsal hippocampus






frontal cortex


tumor necrosis factor-α


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  1. 1.
    McEwen, B.S., Neuroimage, 2009, vol. 47, pp. 911–913.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Armario, A., Martí, O., Vallès, A., Dal-Zotto, S., and Ons, S., Ann. NY Acad. Sci., 2004, vol. 1018, pp. 162–172.CrossRefPubMedGoogle Scholar
  3. 3.
    Armario, A., Escorihuela, R., and Nadal, R., Neurosci. Biobehav. Rev., 2008, vol. 32, pp. 1121–1135.CrossRefPubMedGoogle Scholar
  4. 4.
    Fernandes, G., Perks, P., Cox, N., Lightman, S., Ingram, C., and Shanks, N., J. Neuroendocrinol., 2002, vol. 14, pp. 593–602.CrossRefPubMedGoogle Scholar
  5. 5.
    Ulrich-Lai, Y.M. and Herman, J.P., Nat. Rev. Neurosci., 2009, vol. 10, pp. 397–409.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fanselow, M. and Dong, H., Neuron, 2010, vol. 65, pp. 7–19.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Segal, M., Richter-Levin, G., and Maggio, N., Hippocampus, 2010, vol. 20, pp. 1332–1338.CrossRefPubMedGoogle Scholar
  8. 8.
    Feldman, S. and Weidenfeld, J., Brain Res., 2001, vol. 911, pp. 22–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Reul, J. and de Kloet, E., Endocrinology, 1985, vol. 117, pp. 2505–2511.CrossRefPubMedGoogle Scholar
  10. 10.
    Herman, J., Cell. Mol. Neurobiol., 1993, vol. 13, pp. 349–372.CrossRefPubMedGoogle Scholar
  11. 11.
    Johnson, J., Campisi, J., Sharkey, C., Kennedy, S., Nickerson, M., Greenwood, B., and Fleshner, M., Neuroscience, 2005, vol. 135, pp. 1295–1307.CrossRefPubMedGoogle Scholar
  12. 12.
    Ryabinin, A., Wang, Y., and Finn, D., Pharmacol. Biochem. Behav., 1999, vol. 63, pp. 143–151.CrossRefPubMedGoogle Scholar
  13. 13.
    Asanuma, M. and Ogawa, N., Rev. Neurosci., 1994, vol. 5, pp. 171–178.PubMedGoogle Scholar
  14. 14.
    Miranda, K., Espey, M., and Wink, D., Nitric Oxide Biol. Chem., 2001, vol. 5, pp. 62–71.CrossRefGoogle Scholar
  15. 15.
    Verde, V., Fogliano, V., Ritieni, A., Maiani, G., Morisco, F., and Caporaso, N., Free Radic. Res., 2002, vol. 36, pp. 869–873.CrossRefPubMedGoogle Scholar
  16. 16.
    Myhre, O., Andersen, J., Aarnes, H., and Fonnum, F., Biochem. Pharmacol., 2003, vol. 65, pp. 1575–1582.CrossRefPubMedGoogle Scholar
  17. 17.
    Dallman, M. and Jones, M., Endocrinology, 1973, vol. 92, pp. 1367–1375.CrossRefPubMedGoogle Scholar
  18. 18.
    Fanselow, M. and Dong, H., Neuron, 2010, vol. 65, pp. 7–19.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Moncada, S., Palmer, R., and Higgs, E., Pharmacol. Rev., 1991, vol. 43, pp. 109–142.PubMedGoogle Scholar
  20. 20.
    Carda, A., Marchi, K., Rizzi, E., Mecawi, A., Antunes-Rodrigues, J., Padovan, C., and Tirapelli, C., Stress, 2015, vol. 18, pp. 233–243.CrossRefPubMedGoogle Scholar
  21. 21.
    Sayre, L., Perry, G., and Smith, M., Chem. Res. Toxicol., 2008, vol. 21, pp. 172–188.CrossRefPubMedGoogle Scholar
  22. 22.
    Zlatkovic, J., Todorovic, N., Boškovic, M., Pajovic, S., Demajo, M., and Filipovic, D., Mol. Cell. Biochem., 2014, vol. 393, pp. 43–57.CrossRefPubMedGoogle Scholar
  23. 23.
    Haddad, J., Saadé, N., and Safieh-Garabedian, B., J. Neuroimmunol., 2002, vol. 133, pp. 1–19.CrossRefPubMedGoogle Scholar
  24. 24.
    Sorrells, S., Caso, J., Munhoz, C., and Sapolsky, R., Neuron, 2009, vol. 64, pp. 33–39.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gadek-Michalska, A., Tadeusz, J., Rachwalska, P., Spyrka, J., and Bugajski, J., Pharmacol. Rep., 2011, vol. 63, pp. 1393–1403.CrossRefPubMedGoogle Scholar
  26. 26.
    Advani, T., Koek, W., and Hensler, J., Int. J. Neuropsychopharmacol., 2009, vol. 12, pp. 583–588.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • S. V. Freiman
    • 1
  • M. V. Onufriev
    • 1
    Email author
  • M. Yu. Stepanichev
    • 1
  • Yu. V. Moiseeva
    • 1
  • N. A. Lazareva
    • 1
  • N. V. Gulyaeva
    • 1
  1. 1.Institute of Higher Nervous Activity and NeurophysiologyRussian Academy of SciencesMoscowRussia

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