Dişi Sıçanlarda Üç Farklı Stres Modelinin Anksiyete ve/veya Depresyon Benzeri Davranışlara Etkilerinin Karşılaştırılması

Yıl 2019, Cilt: 9 Sayı: 1, 131 - 140, 20.03.2019

Zafer Şahin Aynur Koç Raviye Özen Koca Hatice Solak Alpaslan Özkürkçüler Pınar Çakan Zülfikare İşık Solak Görmüş Selim Kutlu

Öz

Amaç: Mevcut çalışmada yetişkin dişi sıçanlarda üç farklı
stres protokolünün anksiyete/depresyon benzeri davranışlara etkisinin
kıyaslanması amaçlanmıştır.

Gereç ve Yöntemler: Yetişkin Wistar sıçanlar kontrol, immobilizasyon
stresi-1 (günlük 45 dakika) immobilizasyon stresi-2 (günlük iki kez 45 dakika)
ve sosyal izolasyon (metabolik kafeste) olarak rastgele dört gruba ayrıldı (n =
8). Stres protokolleri 10 gün boyunca uygulandı ve depresyon/anksiyete
davranışları, hayvanlar diöstrüs dönemindeyken, açık alan ve zorunlu yüzme
testi ile değerlendirildi. Aynı testleri 10 günlük dinlenme süresinden sonra
tekrarlandı.

Bulgular: Açık alan testinde, merkez alanda geçirilen zaman
immobilizasyon stresi-2 ve sosyal izolasyon gruplarında azaldı (p<0.05).
Toplam kat edilen mesafe immobilizasyon stresi-1 (p<0.01) ve sosyal
izolasyon (p<0.05) gruplarında daha düşüktü. Sosyal izolasyon grubunun şahlanma davranışı (p < 0.05) kontrol grubuna göre
düşüktü. İmmobilizasyon stresi-1 ve sosyal izolasyon gruplarında yüzme
davranışı azalırken (p < 0.01),
immobilizasyon davranışı kontrol grubuna göre artış göstermişti (p <0.05).
İkinci testlerde, merkezi alanda geçirilen süre immobilizasyon stresi-1 ve
immobilizasyon stresi-2 gruplarında daha düşüktü (p <0.05 ve p <0.01).
İmmobilizasyon stresi-1 (p <0.001) ve sosyal izolasyon gruplarında (p <0.01) yüzme davranışı azalırken,
immobilizasyon süresi kontrole kıyasla artmıştı (p <0.001).

Sonuç: İmmobilizasyon stresi-1 ve metabolik kafeste sosyal
izolasyon protokolü uygulanan erişkin dişi sıçanlarda depresyon benzeri
davranışların daha baskın olduğu söylenebilir. 

Anahtar Kelimeler

immobilizasyon stresi, sosyal izolasyon, depresyon, anksiyete, dişi sıçan

Comparison of Effects of Three Distinct Stress Models on Anxiety and/or Depression-Related Behaviors in Female Rats

Öz

Objective: The aim of the present study was to compare the
effects of three distinct stress protocols on anxiety/depression-related
behaviors in adult female rats.

Material
and Methods: Adult Wistar
rats were randomly divided into four groups (n=8) as control, immobilization
stress-1 (daily 45 minutes) immobilization stress-2 (daily twice 45 minutes)
and social isolation (rats were housed in a metabolic cage). Stress protocols
were performed for a period of 10 days. When the animals were in diestrus,
depression/anxiety-like behaviors were evaluated by the open field test and
forced swimming test. The same tests were repeated after a 10-day rest period.

Results: In the open field test, a percentage of time spent
in the central area was lower in the immobilization stress-2 and social
isolation (p<0.05) groups and total distance was lower in the immobilization
stress-1 (p<0.01) and the social isolation groups (p<0.05). Rearing score
was lower in the social isolation group (p<0.05). Swimming behaviors were lower
(p<0.01), and immobility durations were higher (p<0.05) in the
immobilization stress-1 and social isolation groups. In the second tests, time
spent in the central area was lower in the immobilization stress-1 (p<0.05)
and the immobilization stress-2 (p<0.01) groups. Swimming behaviors were
lower and immobility behaviors were higher in the immobilization stress-1 group
(p<0.001) and the social isolation group (p<0.01 and p<0.001,
respectively).

Conclusion: We suggest that depression-like behaviors are more
dominant in the immobilization stress-1 and social isolation groups of adult
female rats.

Anahtar Kelimeler

immobilization stress, social isolation, depression, anxiety, female rat

Kaynakça

• Schneiderman N, Ironson G, Siegel SD. Stress and health: psychological, behavioral, and biological determinants. Annu Rev Clin Psychol 2005; 1:607-28.
• Kvetnansky R, Jelokova J, Rusnak M, Dronjak S, Serova B, Nankova B, et al. Novel stressors exaggerate tyrosine hydroxylase gene expression in the adrenal medulla of rats exposed to long-term cold stress, in: R. Kvetnansky (Ed.) Stress: Neural, Endocrine and Molecular studies, Taylor and Francis, London, Edition 1, 2002, 121-128.
• Pacak K, Kvetnansky R, Palkovits M, Fukuhara K, Yadid G, Kopin IJ, et al. Adrenalectomy augments In-vivo release of norepinephrine in the paraventricular nucleus during immobilization stress. Endocrinology 1993; 133:1404-1410.
• Venihaki M, Gravanis A, Margioris AN. Comparative study between normal rat chromaffin and PC12 rat pheochromocytoma cells: Production and effects of Corticotropin Releasing Hormone (CRH). Endocrinology 1997; 138:698-704.
• Anisman H, Matheson K. Stress, depression, and anhedonia: Caveats concerning animal models. Neuroscience Biobehavioral Reviews 2005; 29:525-546.
• McEwen BS. Understanding the potency of stressful early life experiences on brain and body function. Metabolism 2008; 57:11-15.
• Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, et al. Lifetime and 12 month prevalence of DSM-III-R-psychiatric disorders in the United States: results from the national comorbidity survey. Arch Gen Psychiatry 1994; 51:8-19.
• Murray CJ, Lopez AD. Gobal mortality, disability and the contribution of risk factors: global burden of disease study. Lancet 1997; 349:1436-42.
• Palanza P. Animal models of anxiety and depression: how are females different? Neurosci Biobehav Rev 2001; 25:219-33.
• Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, et al. Schizophrenia: manifestations, incidence and course in different cultures: a WHO ten country study. Cambridge: Cambridge University Press, 1992.
• Hanna EZ, Grant BF. Gender differences in DSM-IV alcohol use disorders and major depression as distributed in the general population: clinical implications. Compr Psychiatry 1997; 38:201-12.
• Gater R, Tansella M, Korten A, Tiemens BG, Mavreas VG, Olatawura MO. Sex differences in the prevalence and detection of depressive and anxiety disorders in general health care settings-Report from the World Health Organization collaborative study on Psychological Problems in General Health Care. Archiv Gen Psychiatry 1998; 55:405-13.
• Maeng LY, Milad MR. Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav 2015; 76:106-17.
• Leuner B, Mendolia-Loffredo S, Shors TJ. Males and females respond differently to controllability and antidepressant treatment. Biol Psychiatry 2004; 56(12):964-70.
• Altemus M, Sarvaiya N, Neill Epperson C. Sex differences in anxiety and depression clinical perspectives. Front Neuroendocrinol 2014; 35:320-30.
• Stepanichev M, Dygalo NN, Grigoryan G, Shishkina GT, Gulyaeva N. Rodent models of depression: neurotrophic and neuroinflammatory biomarkers. Biomed Res Int 2014; 2014:932757.
• Krishnan V, Nestler EJ. Animal models of depression: molecular perspectives. Curr Top Behav Neurosci 2011; 7:121-47.
• Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R. A review on animal models for screening potential anti-stress agents. Neurol Sci 2011; 32:993-1005.
• Kvetnansky R, Mikulaj L. Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology 1970; 87:738-43.
• Buynitsky T, Mostofsky DI. Restraint stress in biobehavioral research: Recent developments. Neurosci Biobehav Rev 2009; 33:1089-98.
• Bali A, Jaggi AS. Preclinical experimental stress studies: protocols, assessment and comparison. Eur J Pharmacol 2015; 746:282-92.
• Sahin Z, Solak H, Koc A, Ozen Koca R, Ozkurkculer A, Cakan P, et al. Long-term metabolic cage housing increases anxiety/depression-related behaviours in adult male rats. Arch Physiol Biochem. 2018 Feb 20:1-6. doi: 10.1080/13813455.2018.1441314.
• Ollson IAS, Westlund K. More than numbers matter: The effect of social factors on behaviour and welfare of laboratory rodents and non-human primates. Appl Anim Behav Sci 2007; 103:229–254.
• Zymantiene J, Zelvyte R, Oberauskas V, Spancerniene U. Influence of Metabolic Cage on Wistar Rat Physiological State. Mac Vet Rev 2016; 39:33-38.
• Pinelli CJ, Leri F, Turner PV. Long Term Physiologic and Behavioural Effects of Housing Density and Environmental Resource Provision for Adult Male and Female Sprague Dawley Rats. Animals (Basel) 2017; 7:E44.
• Whittaker AL, Lymn KA, Howarth GS. Effects of Metabolic Cage Housing on Rat Behavior and Performance in the Social Interaction Test. J Appl Anim Welf Sci 2016; 19:363-74.
• Cruthirds DF, Siangco AL, Hartman CJ, Sandefur DC, Spencer JM Jr, Dyer CA, et al. Effects of immobilization stress and hormonal treatment on nociception. AANA J 2011; 79:375-80.
• Benchimol de Souza D, Silva D, Marinho Costa Silva C, Barcellos Sampaio FJ, Silva Costa W, Martins Cortez C. Effects of immobilization stress on kidneys of Wistar male rats: a morphometrical and stereological analysis. Kidney Blood Press Res 2011; 34:424-9.
• Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 2003; 463:3-33.
• Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977; 266:730-2.
• Canpolat S, Ulker N, Yardimci A, Bulmus O, Ozdemir G, Sahin Z, et al. Studies on the reproductive effects of chronic treatment with agomelatine in the rat. Eur J Pharmacol 2016; 770:33-9.
• Simon P, Dupuis R, Costentin J. Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 1994; 61:59–64.
• Henderson ND, Turri MG, DeFries JC, Flint J. QTL analysis of multiple behavioral measures of anxiety in mice. Behav Genet 2004; 34:267-93.
• Goswami S, Rodríguez-Sierra O, Cascardi M, Paré D. Animal models of post-traumatic stress disorder: face validity. Front Neurosci 2013;7:89.
• Schöner J, Heinz A, Endres M, Gertz K, Kronenberg G. Post-traumatic stress disorder and beyond: an overview of rodent stress models. J Cell Mol Med 2017;21(10):2248-2256.
• Maldonado R, Smadja C, Mazzucchelli C, Sassone-Corsi P. Altered emotional and locomotor responses in mice deficient in the transcription factor CREM. Proc Natl Acad Sci USA 1999; 96:14094-9.
• Fuchs E, Fliugge G. Experimental animal models for the simulation of depression and anxiety. Dialogues Clin Neurosci 2006; 8:323-33.
• Van Abeelen JHF., 1975. Genetic Analysis of Behavioural Responses to Novelty in Mice. Nature 1975; 254:239-241.
• Sestakova N, Puzserova A, Kluknavsky M, Bernatova I. Determination of motor activity and anxiety-related behaviour in rodents: methodological aspects and role of nitric oxide. Interdiscip Toxicol 2013; 6:126-35.
• Thompson RF, Spencer WA. Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 1966; 73:16–43.
• Cryan JF, Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nature reviews. Drug discovery 2005; 4:775–790.
• Cryan JF, Mombereau C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 2004; 9:326-57.
• Cryan JF, Page ME, Lucki I. Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology (Berl) 2005; 182:335-44.
• Song X, Tian H, Bressler J, Pruett S, Pope C. Acute and repeated restraint stress have little effect on pyridostigmine toxicity or brain regional cholinesterase inhibition in rats. Toxicol Sci 2002; 69:157-64.
• Vyas A, Chattarji S. Modulation of different states of anxiety-like behavior by chronic stress. Behavioral Neuroscience 2004; 118:1450-1454.
• Ampuero E, Luarte A, Santibañez M, Varas-Godoy M, Toledo J, Diaz-Veliz G, et al. Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker. Int J Neuropsychopharmacol 2015; 18(10):pyv038.
• Xing B, Liu P, Jiang WH, Liu F, Zhang H, Cao GF, et al. Effects of immobilization stress on emotional behaviors in dopamine D3 receptor knockout mice. Behav Brain Res 2013; 243:261-6.
• Padovan CM, Guimara˜es FS. Restraint-induced hypoactivity in an elevated plus-maze. Braz J Med Biol Res 2000; 33:79-83.
• Campos AC, Ferreira FR, Guimara˜es FS, Lemos JI. Facilitation of endocannabinoid effects in the ventral hippocampus modulates anxiety-like behaviors depending on previous stress experience. Neuroscience 2010; 167:238-46.