Skip to main content
SpringerLink
Log in

Investigation of Effects of Two Chronic Stress Protocols on Depression-Like Behaviors and Brain Mineral Levels in Female Rats: an Evaluation of 7-Day Immobilization Stress

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

We aimed to investigate the effects of two different chronic immobilization stress protocols on depression-related behaviors and brain mineral levels. Adult female Wistar albino rats were divided into 3 groups as follows (n = 10/group): control, immobilization stress-1 (45 min daily for 7 days), and immobilization stress-2 (45 min twice a day for 7 day). Stress-related behavior was evaluated by means of the forced swimming test (FST) and open field test (OFT). Minerals were analyzed using an inductively coupled plasma mass spectrometer. In the FST, swimming and immobility were significantly lower in the immobilization stress-1 and immobilization stress-2 groups. The climbing duration of the immobilization stress-2 group was higher than the control group. In the OFT, percentage of time spent in the central area was significantly lower in the immobilization stress-1 and immobilization stress-2 groups. Values of latency to center area, rearing, and grooming did not significantly differ between groups. In the immobilization stress-1 group, zinc was lower, and iron, copper, and manganese were higher than the control group. In the immobilization stress-2 group, copper and manganese were higher, and phosphate was lower than the control group. Our results showed that depression-related behaviors were more dominant in the immobilization stress-1 group. A decrease in the brain zinc level was valid only for the immobilization stress-1 group. These results point to the role of low brain zinc levels in the pathophysiology of depression.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Anisman H, Matheson K (2005) Stress, depression, and anhedonia: caveats concerning animal models. Neurosci Biobehav Rev 29(4–5):525–546

    PubMed  Google Scholar 

  2. Schneiderman N, Ironson G, Siegel SD (2005) Stress and health: psychological, behavioral, and biological determinants. Annu Rev Clin Psychol 1:607–628

    PubMed  PubMed Central  Google Scholar 

  3. McEwen BS (2008) Understanding the potency of stressful early life experiences on brain and body function. Metabolism 57(Suppl 2):S11–S15

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Şahin Z, Özkürkçüler A, Koç A et al (2019) An evaluation of the effects of two chronic immobilization stress protocols on depression/anxiety-related behavior in male rats. ACU Sağlık Bil Derg 10(3):535–541

    Google Scholar 

  5. Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R (2011) A review on animal models for screening potential anti-stress agents. Neurol Sci 32:993–1005

    PubMed  Google Scholar 

  6. Bali A, Jaggi AS (2015) Preclinical experimental stress studies: protocols, assessment and comparison. Eur J Pharmacol 746:282–292

    CAS  PubMed  Google Scholar 

  7. Sahin Z, Koc A, Ozen Koca R et al (2019) Comparison of effects of three distinct stress models on anxiety- and depression-related behaviors in female rats. Sakarya Med J 9(1):131–140

    Google Scholar 

  8. Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJL, Vos T, Whiteford HA (2013) Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med 10(11):e1001547

    PubMed  PubMed Central  Google Scholar 

  9. Depression and Other Common Mental Disorders: Global Health Estimates (2017). Geneva: World Health Organization. Licence: CC BY-NC-SA 3.0 IGO.p:8–12

  10. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163(1):28–40

    PubMed  Google Scholar 

  11. Gartlehner G, Hansen RA, Morgan LC, et al (2011) Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review. (prepared by the RTI International–University of North Carolina Evidence-based Practice Center, Contract No. 290-2007-10056-I.) AHRQ Publication No. 12-EHC012-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2011

  12. Wilson S, Vaidyanathan U, Miller MB, McGue M, Iacono WG (2014) Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course? Dev Psychopathol 26:1477–1493

    PubMed  PubMed Central  Google Scholar 

  13. Fraga CG (2005) Relevance, essentiality and toxicity of trace elements in human health. Mol Asp Med 26:235–244

    CAS  Google Scholar 

  14. Alimonti A, Ristori G, Giubilei F, Stazi MA, Pino A, Visconti A, Brescianini S, Monti MS, Forte G, Stanzione P, Bocca B, Bomboi G, D’Ippolito C, Annibali V, Salvetti M, Sancesario G (2007) Serum chemical elements and oxidative status in Alzheimer’s disease, Parkinson disease and multiple sclerosis. Neurotoxicology 28:450–456

    CAS  PubMed  Google Scholar 

  15. Mustak MS, Rao TS, Shanmugavelu P et al (2008) Assessment of serum macro and trace element homeostasis and the complexity of inter-element relations in bipolar mood disorders. Clin Chim Acta 394(1-2):47–53

    CAS  PubMed  Google Scholar 

  16. Nahar Z, Azad MA, Rahman MA et al (2010) Comparative analysis of serum manganese, zinc, calcium, copper and magnesium level in panic disorder patients. Biol Trace Elem Res 133:284–290

    CAS  PubMed  Google Scholar 

  17. Shohag H, Ullah A, Qusar S, Rahman M, Hasnat A (2012) Alterations of serum zinc, copper, manganese, iron, calcium, and magnesium concentrations and the complexity of interelement relations in patients with obsessive-compulsive disorder. Biol Trace Elem Res 148:275–280

    CAS  PubMed  Google Scholar 

  18. Błażewicz A, Liao KY, Liao HH et al (2017) Alterations of hair and nail content of selected trace elements in nonoccupationally exposed patients with chronic depression from different geographical regions. Biomed Res Int 2017:3178784

    PubMed  PubMed Central  Google Scholar 

  19. Wang J, Um P, Dickerman BA, Liu J (2018) Zinc, magnesium, selenium and depression: a review of the evidence, potential mechanisms and implications. Nutrients 10(5)

  20. Murck H (2002) Magnesium and affective disorders. Nutr Neurosci 5:375–389

    CAS  PubMed  Google Scholar 

  21. Sahin Z, Solak H, Koc A, Ozen Koca R, Ozkurkculer A, Cakan P, Solak Gormus ZI, Kutlu S, Kelestimur H (2019) Long-term metabolic cage housing increases anxiety/depression-related behaviours in adult male rats. Arch Physiol Biochem 125(2):122–127

    CAS  PubMed  Google Scholar 

  22. Rattanachongkiat S, Millward GE, Foulkes ME (2004) Determination of arsenic species in fish, crustacean and sediment samples from Thailand using high performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICPMS). J Environ Monit 6(4):254–261

    CAS  PubMed  Google Scholar 

  23. De Blas BI, Sanz Castro R, López Riquelme N, Tormo Díaz C, Apraiz Goyenaga D (2007) Optimization of the trace element determination by ICP-MS in human blood serum. J Trace Elem Med Biol 21(Suppl 1):14–17

    Google Scholar 

  24. Castagné V, Moser P, Roux S, Porsolt RD (2011) Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci Chapter 8:Unit 8.10A

  25. Canpolat S, Ulker N, Yardimci A, Bulmus O, Ozdemir G, Sahin Z, Ercan Z, Serhatlioglu I, Kacar E, Ozcan M, Turk G, Ozkan Y, Atmaca M, Yilmaz B, Kelestimur H (2016) Studies on the reproductive effects of chronic treatment with agomelatine in the rat. Eur J Pharmacol 770:33–39

    CAS  PubMed  Google Scholar 

  26. Cryan JF, Mombereau C (2004) In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9:326–357

    CAS  PubMed  Google Scholar 

  27. Cryan JF, Page ME, Lucki I (2005) Differential behavioral effects of the anti-depressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology 182:335–344

    CAS  PubMed  Google Scholar 

  28. Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455:178–182

    CAS  PubMed  Google Scholar 

  29. Suvrathan A, Tomar A, Chattarji S (2010) Effects of chronic and acute stress on rat behaviour in the forced-swim test. Stress 13:533–540

    PubMed  Google Scholar 

  30. Lee B, Yun HY, Shim I, Lee H, Hahm DH (2012) Bupleurum falcatum prevents depression and anxiety-like behaviors in rats exposed to repeated restraint stress. J Microbiol Biotechnol 22:422–430

    PubMed  Google Scholar 

  31. Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I (1999) Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology 147:162–167

    CAS  PubMed  Google Scholar 

  32. Lam VYY, Raineki C, Takeuchi LE, Ellis L, Woodward TS, Weinberg J (2018) Chronic stress alters behavior in the forced swim test and underlying neural activity in animals exposed to alcohol prenatally: sex- and time-dependent effects. Front Behav Neurosci 12:42

    PubMed  PubMed Central  Google Scholar 

  33. Anyan J, Amir S (2018) Too depressed to swim or too afraid to stop? A reinterpretation of the forced swim test as a measure of anxiety-like behavior. Neuropsychopharmacology 43(5):931–933

    PubMed  Google Scholar 

  34. American Psychiatric Association DSM-5 (2013) Diagnostic and statistical manual of mental disorders, Fifth edn. APA, Washington DC

    Google Scholar 

  35. Şahin Z, Özen Koca R, Solak H et al (2019) Comparison of the effects of immobilization stress and chronic mild stress models on depression-related behaviors in female rats: an assessment of a 10-day stress period. FU Med J Health Sci 33(3):153–157

    Google Scholar 

  36. Belovicova K, Bogi E, Csatlosova K, Dubovicky M (2017) Animal tests for anxiety-like and depression-like behavior in rats. Interdiscip Toxicol 10:40–43

    PubMed  Google Scholar 

  37. Herzog DP, Wegener G, Lieb K, Müller MB, Treccani G (2019) Decoding the mechanism of action of rapid-acting antidepressant treatment strategies: does gender matter? Int J Mol Sci 20:E949

    PubMed  Google Scholar 

  38. Ampuero E, Luarte A, Santibañez M et al (2015) Two chronic stress models based on movement restriction in rats respond selectively to antidepressant drugs: aldolase C as a potential biomarker. Int J Neuropsychopharmacol 18(10):pyv038

    PubMed  PubMed Central  Google Scholar 

  39. Son H, Yang JH, Kim HJ, Lee DK (2019) A chronic immobilization stress protocol for inducing depression-like behavior in mice. J Vis Exp 147. https://doi.org/10.3791/59546

  40. Ames BN, Elson-Schwab I, Silver EA (2002) High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased km): relevance to genetic disease and polymorphisms. Am J Clin Nutr 75:616–658

    CAS  PubMed  Google Scholar 

  41. Tokdemir M (2003) Blood zinc and copper concentrations in criminal and non-criminal schizophrenic men. Arch Androl 49:365–368

    CAS  PubMed  Google Scholar 

  42. Walsh WJ, Issacson HR, Hall A (1997) Elevated blood copper/zinc ratios in assaultive young males. Physiol Behav 62:327–329

    CAS  PubMed  Google Scholar 

  43. Hubbard PC, Lummis SCR (2000) Zn2+ enhancement of the recombinant 5-HT(3) receptor is modulated by divalent cations. Eur J Pharmacol 394:189–197

    CAS  PubMed  Google Scholar 

  44. Plum LM, Rink L, Haase H (2010) The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 7(4):1342–1365

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Szewczyk B, Poleszak E, Wlaź P, Wróbel A, Blicharska E, Cichy A, Dybała M, Siwek A, Pomierny-Chamioło L, Piotrowska A, Brański P, Pilc A, Nowak G (2009) The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test. Prog Neuro-Psychopharmacol Biol Psychiatry 33(2):323–329

    CAS  Google Scholar 

  46. Jung KI, Ock SM, Chung JH, Song CH (2010) Associations of serum Ca and Mg levels with mental health in adult women without psychiatric disorders. Biol Trace Elem Res 133:153–161

    CAS  PubMed  Google Scholar 

  47. Barragan-Rodriguez L, Rodriguez-Moran M, Guerrero-Romero F (2007) Depressive symptoms and hypomagnesemia in older diabetic subjects. Arch Med Res 38(7):752–756

    CAS  PubMed  Google Scholar 

  48. Sowa-Kucma M, Szewczyk B, Sadlik K et al (2013) Zinc, magnesium and nmda receptor alterations in the hippocampus of suicide victims. J Affect Disord 151(3):924–931

    CAS  PubMed  Google Scholar 

  49. Szewczyk B, Szopa A, Serefko A, Poleszak E, Nowak G (2018) The role of magnesium and zinc in depression: similarities and differences. Magnes Res 31(3):78–89

    CAS  PubMed  Google Scholar 

  50. Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C (2017) Role of magnesium supplementation in the treatment of depression: a randomized clinical trial. PLoS One 12:e0180067

    PubMed  PubMed Central  Google Scholar 

  51. Serefko A, Szopa A, Wlaź P, Nowak G, Radziwoń-Zaleska M, Skalski M, Poleszak E (2013) Magnesium in depression. Pharmacol Rep 65:547–554

    CAS  PubMed  Google Scholar 

  52. Li Y, Zheng Y, Qian J, Chen X, Shen Z, Tao L, Li H, Qin H, Li M, Shen H (2012) Preventive effects of zinc against psychological stress-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats. Biol Trace Elem Res 147:285–291

    CAS  PubMed  Google Scholar 

  53. Ferreira A, Neves P, Gozzelino R (2019) Multilevel impacts of Iron in the brain: the cross talk between neurophysiological mechanisms, cognition, and social behavior. Pharmaceuticals (Basel) 12(3):126

    CAS  Google Scholar 

  54. Lehmann ML, Weigel TK, Elkahloun AG, Herkenham M (2017) Chronic social defeat reduces myelination in the mouse medial prefrontal cortex. Sci Rep 7:46548

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Zuo LJ, Yu SY, Hu Y, Wang F, Piao YS, Lian TH, Yu QJ, Wang RD, Li LX, Guo P, du Y, Zhu RY, Jin Z, Wang YJ, Wang XM, Chan P, Chen SD, Wang YJ, Zhang W (2016) Serotonergic dysfunctions and abnormal iron metabolism: relevant to mental fatigue of Parkinson disease. Sci Rep 6(1):19

    PubMed  PubMed Central  Google Scholar 

  56. Beard JL, Connor JR (2003) Iron status and neural functioning. Annu Rev Nutr 23:41–58

    CAS  PubMed  Google Scholar 

  57. Nnah IC, Wessling-Resnick M (2018) Brain Iron homeostasis: a focus on microglial iron. Pharmaceuticals (Basel) 11(4)

  58. Takeda A (2000) Movement of zinc and its functional significance in the brain. Brain Res Brain Res Rev 34(3):137–148

    CAS  PubMed  Google Scholar 

  59. Crayton J, Walsh W (2007) Elevated serum copper levels in women with a history of post-partum depression. J Trace Elem Med Biol 14:17–21

    Google Scholar 

  60. Russo AJ (2011) Decreased zinc and increased copper in individuals with anxiety. Nutr Metab Insights 4:1–5

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Maddock RJ, Moses JA Jr, Roth WT, King R, Murchison A, Berger PA (1987) Serum phosphate and anxiety in major depression. Psychiatry Res 22(1):29–36

    CAS  PubMed  Google Scholar 

  62. Thi Thu Nguyen T, Miyagi S, Tsujiguchi H et al (2019) Association between lower intake of minerals and depressive symptoms among elderly Japanese women but not men: findings from Shika Study. Nutrients 11(2)

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Z. Sahin & O. F. Kalkan

  2. Department of Physiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    A. Ozkurkculer, R. Ozen Koca, H. Solak, Z. I. Solak Gormus & S. Kutlu

  3. Department of Chemistry, Faculty of Science and Art, Adiyaman University, Adiyaman, Turkey

    A. Ozkaya

  4. Department of Physiology, Faculty of Medicine, Hitit University, Corum, Turkey

    A. Koc

Authors
  1. Z. Sahin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Ozkurkculer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. F. Kalkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Ozkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Koc
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Ozen Koca
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Solak
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Z. I. Solak Gormus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Kutlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z. Sahin.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This study has been approved by the Ethics Committee of the Necmettin Erbakan University Local Ethics Committee for Experimental Animals (2016-057).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahin, Z., Ozkurkculer, A., Kalkan, O.F. et al. Investigation of Effects of Two Chronic Stress Protocols on Depression-Like Behaviors and Brain Mineral Levels in Female Rats: an Evaluation of 7-Day Immobilization Stress. Biol Trace Elem Res 199, 660–667 (2021). https://doi.org/10.1007/s12011-020-02160-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02160-5

Keywords

Search

Navigation