The Effect of Maternal Separation on Anxiety Behavior in of White Mice (Mus Musculus L.) Male Swiss Webster Strain
Main Article Content
Introduction. Maternal separation (MS) is a commonly utilized model of early-life stress to explain the influence on brain development and psychological behavior. MS has been demonstrated to elevate the likelihood of developing anxiety disorders as a consequence of alterations in hypothalamic- pituitary-adrenal (HPA) functionality and neurotransmitter levels. This study aimed to evaluate the impact of maternal separation (MS) duration on anxiety behavior in male Swiss Webster strain white mice (Mus musculus L.). Methods. The study used a true experimental method with a posttest- only control group design. A total of 28 male mice aged 2 days were randomly assigned to one of four groups: a control group that did not undergo maternal separation (MS) and three MS treatment groups with a duration of 2 hours, 4 hours, and 6 hours per day for 21 days. Anxiety behavior was evaluated using the Elevated Plus Maze (EPM), with the number and duration of entries into the closed and open arms serving as the primary analysis metrics. The data were analyzed using one-way ANOVA and post-hoc LSD statistical tests. The duration of MS significantly impacted the anxiety behavior of the mice. Results. The MS groups of 2, 4 and 6 hours demonstrated a notable increase in the number and duration of entries into the closed arm in comparison to the control group (p < 0.05), which is indicative of increased anxiety. In contrast, the number of entries into the open arm decreased in the 6 h MS group compared to the control. Conclusion. The results indicated that MS negatively affected the anxiety behavior of mice, with longer duration exacerbating the trend.
Keywords:
Anxiety
Maternal separation
Elevated plus maze
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2. Meng X, Bao B, Yue G. Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis. Heliyon. 2023 Aug;9(8):e18469.
3. Daskalakis NP, Bagot RC, Parker KJ, Vinkers CH, De Kloet ER. The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology. 2013 Sep;38(9):1858–73.
4. Pebriansyah R, Suryawan A, Setyoningrum RA. The effect of maternal separation during the mothers taking medical residency education program to behavior- psychosocial- emotional of children. YMER 2023;22(02):249-59.
5. Puspitasari I, Wati DE. Strategi parent-school partnership: upaya preventif separation anxiety disorder pada anak usia dini. Yaa Bunayya: Jurnal Pendidikan Anak Usia Dini. 2018;2(1):49-60.
6. Enoch MA. The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology. 2011 Mar;214(1):17–31.
7. He T, Guo C, Wang C, Hu C, Chen H. Effect of early life stress on anxiety and depressive behaviors in adolescent mice. Brain and Behavior. 2020 Mar;10(3):e01526.
8. Jarrar Q, Ayoub R, Alhussine K, Goh KW, Moshawih S, Ardianto C, et al. Prolonged Maternal Separation Reduces Anxiety State and Increases Compulsive Burying Activity in the Offspring of BALB/c Mice. JPM. 2022 Nov 17;12(11):1921.
9. He B, Fan J, Liu N, Li H, Wang Y, Williams J, et al. Depression risk of ‘left-behind children’ in rural China. Psychiatry Research. 2012 Dec;200(2–3):306–12.
10. Sung YH, Shin MS, Cho S, Baik HH, Jin BK, Chang HK, et al. Depression-like state in maternal rats induced by repeated separation of pups is accompanied by a decrease of cell proliferation and an increase of apoptosis in the hippocampus. Neuroscience Letters. 2010 Feb;470(1):86–90.
11. Aguggia JP, Suárez MM, Rivarola MA. Early maternal separation: Neurobehavioral consequences in mother rats. Behavioural Brain Research. 2013 Jul;248:25–31.
12. Videbeck SL. Textbook of Psychiatric Nursing. Jakarta: EGC; 2008.
13. Hock E, McBride S, Gnezda MT. Maternal Separation Anxiety: Mother-Infant Separation from the Maternal Perspective. Child Development. 1989 Aug;60(4):793.
14. Ehrenreich JT, Santucci LC, Weiner CL. Separation anxiety disorder in youth: phenomenology, assessment, and treatment. Psicologia conductual. 2009;16(3):389.
15. Aisa B, Tordera R, Lasheras B, Del Río J, Ramírez MJ. Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats. Psychoneuroendocrinology. 2007 Apr;32(3):256–66.
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17. Komada M, Takao K, Miyakawa T. Elevated Plus Maze for Mice. JoVE. 2008 Dec 22;(22):1088.
18. Knight P, Chellian R, Wilson R, Behnood-Rod A, Panunzio S, Bruijnzeel AW. Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats. Pharmacology Biochemistry and Behavior. 2021 May;204:173168.
19. Wang D, Levine JLS, Avila-Quintero V, Bloch M, Kaffman A. Systematic review and meta- analysis: effects of maternal separation on anxiety-like behavior in rodents. Transl Psychiatry. 2020 Jun 1;10(1):174.
20. Troakes C, Ingram CD. Anxiety behaviour of the male rat on the elevated plus maze: associated regional increase in c-fos mRNA expression and modulation by early maternal separation. Stress. 2009 Jan;12(4):362–9.
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26. Schmidt MV, Levine S, Alam S, Harbich D, Sterlemann V, Ganea K, et al. Metabolic Signals Modulate Hypothalamic-Pituitary-Adrenal Axis Activation During Maternal Separation of the Neonatal Mouse. J Neuroendocrinology. 2006 Nov;18(11):865–74.
27. Cotella EM, Mestres Lascano I, Franchioni L, Levin GM, Suárez MM. Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment. Stress. 2013 Jul 1;16(4):477–81.
28. McEwen BS, Nasca C, Gray JD. Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex. Neuropsychopharmacol. 2016 Jan;41(1):3–23.
29. Ferrara NC, Opendak M. Amygdala circuit transitions supporting developmentally-appropriate social behavior. Neurobiology of Learning and Memory. 2023 May;201:107762.
30. Rincón-Cortés M, Sullivan RM. Early Life Trauma and Attachment: Immediate and Enduring Effects on Neurobehavioral and Stress Axis Development. Front Endocrinol. 2014 Mar 21;5:33.
31. McEwen BS, Morrison JH. The Brain on Stress: Vulnerability and Plasticity of the Prefrontal Cortex over the Life Course. Neuron. 2013 Jul;79(1):16–29.
32. Récamier-Carballo S, Estrada-Camarena E, López-Rubalcava C. Maternal separation induces long-term effects on monoamines and brain-derived neurotrophic factor levels on the frontal cortex, amygdala, and hippocampus: differential effects after a stress challenge. Behavioural Pharmacology. 2017 Oct;28(7):545–57.
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35. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000 Nov;408(6809):239–47.
36. Halliwell B. Oxidative stress and cancer: have we moved forward? Biochemical Journal. 2007 Jan 1;401(1):1–11.
37. Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biology. 2015 Apr;4:180–3.
38. McEwen BS. Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain. Physiological Reviews. 2007 Jul;87(3):873–904
