EFFECTS OF CAFFEINE IN FEMALE RAT MODELS OF DEPRESSION
DOI:
https://doi.org/10.58407/bht.1.25.4Keywords:
rats, depression, caffeine, anhedonia, behavioral reactionsAbstract
Purpose of the research. Assessment of the effect of caffeine on behavioral indicators of female rats in a state of depression induced by methods of unpredictable stress and contagious depression.
Methodology. The study was conducted on white sexually mature female rats weighing 230–300 g (N = 72), divided into six groups: intact; females with depression (method of unpredictable chronic stress); female rats that were given caffeine via gavage at a concentration of 25 mg/kg for 5 weeks; females with depression that were given caffeine; female rats with contagious depression; female rats with contagious depression that were given caffeine. Two validated methods were used to assess depressive behavior: the sucrose preference test and the forced swim test. The sucrose preference test was used to determine anhedonia. The forced swim test evaluated immobilization and climbing to assess helpless behavior and stress adaptation activity. Data were analyzed using a two-way analysis of variance (ANOVA) with Tukey’s post hoc test.
Scientific novelty. For the first time, a comparative study of the effect of caffeine on female rats in two different models of depression was conducted. The results obtained allowed us to evaluate different mechanisms of depressive behavior caused by chronic stress and social factors. The analysis allowed us to determine that the effectiveness of caffeine varies depending on the type of depression.
Conclusions. In female rats in models of unpredictable stress and contagious depression, manifestations of anhedonia were observed, namely, a decrease in sucrose preference compared to the control group. An increase in immobility time and a decrease in climbing were also observed, which indicates the formation of helpless behavior. This shows different neurobiological mechanisms of stress regulation depending on its nature. Caffeine had a pronounced antidepressant effect depending on the model of depression. In females in the model of chronic unpredictable stress, caffeine caused an increase in sucrose preference, a decrease in immobilization time, and an increase in climbing. Still, these indicators remained lower than control values. In females with contagious depression, the effect of caffeine was more pronounced: indicators of sucrose preference and climbing almost reached control values. This may be due to the impact of caffeine on social and emotional aspects of behavior. At the same time, in chronic stress, where changes affect more complex adaptation mechanisms, its effect is less pronounced.
Downloads
References
Bangasser, D. A., & Cuarenta, A. (2021). Sex differences in anxiety and depression: circuits and mechanisms. Nature reviews. Neuroscience, 22(11), 674–684. https://doi.org/10.1038/s41583-021-00513-0
Boyko, M., Kutz, R., Grinshpun, Yu., Zvenigorodsky, V., Gruenbaum, Sh. E., Gruenbaum, B. F., Brotfain, E., Shapira, Y., & Zlotnik, A. (2015) Establishment of an animal model of depression contagion. Behavioral Brain Research, 0, 358–363. https://doi.org/10.1016/j.bbr.2014.12.017
Ferre, S., Ciruela, F., Borycz, J., Solinas, M., Quarta, D., Antoniou, K., Quiroz, C., Justinova, Z., Lluis, C., Franco, R., & Goldberg, S. R. (2008). Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain. Frontiers in bioscience: a journal and virtual library, 13, 2391–2399. https://doi.org/10.2741/2852
Harro, J. (2019). Animal models of depression: pros and cons. Cell and Tissue Research, 377, 5–20. https://doi.org/10.1007/s00441-018-2973-0
Herman, J. P., McKlveen, J. M., Ghosal, S., Kopp, B., Wulsin, A., Makinson, R., Scheimann, J., & Myers, B. (2016). Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. Comprehensive Physiology, 6(2), 603–621. https://doi.org/10.1002/cphy.c150015
Kokras, N., & Dalla, C. (2014). Sex differences in animal models of psychiatric disorders. British journal of pharmacology, 171(20), 4595–4619. https://doi.org/10.1111/bph.12710
Lu, Q., Mouri, A., Yang, Y., Kunisawa, K., Teshigawara, T., Hirakawa, M., Mori, Y., Yamamoto, Y., Libo, Z., Nabeshima, T., & Saito, K. (2019). Chronic unpredictable mild stress-induced behavioral changes are coupled with dopaminergic hyperfunction and serotonergic hypofunction in mouse models of depression. Behavioural brain research, 372, 112053. https://doi.org/10.1016/j.bbr.2019.112053
Okeowo, O. M., Oke, O. O., David, G. O., & Ijomone, O. M. (2023). Caffeine Administration Mitigates Chronic Stress-Induced Behavioral Deficits, Neurochemical Alterations, and Glial Disruptions in Rats. Brain sciences, 13(12), 1663. https://doi.org/10.3390/brainsci13121663
Pareek, V., Shah, S., Sharma, B., Kumar, S., & Sharma, L. (2024). Coffee and the brain: A comprehensive review of its neurological and psychiatric effects. Journal of the Indian Academy of Geriatrics, 20(1), 34–39. https://doi.org/10.4103/jiag.jiag_53_23
Planchez, B., Surget, A., & Belzung, C. (2019). Animal models of major depression: drawbacks and challenges. Journal of neural transmission (Vienna, Austria: 1996), 126(11), 1383–1408. https://doi.org/10.1007/s00702-019-02084-y
Primo, M. J., Fonseca-Rodrigues, D., Almeida, A., Teixeira, P. M., & Pinto-Ribeiro, F. (2023). Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents. European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology, 77, 80–92. https://doi.org/10.1016/j.euroneuro.2023.08.496
Sharma, V., Sharma, A., Verma, K., Gaur, P., Kaushik, R., & Abdali, B. (2023). A comprehensive review on pharmacological potentials of caffeine. Journal of Applied Pharmaceutical Sciences and Research, 6(3), 16-26. https://doi.org/10.31069/japsr.v6i3.04
Slattery, D. A., & Cryan, J. F. (2017). Modelling depression in animals: at the interface of reward and stress pathways. Psychopharmacology, 234(9-10), 1451–1465. https://doi.org/10.1007/s00213-017-4552-6
Slavich, G. M., & Sacher, J. (2019). Stress, sex hormones, inflammation, and major depressive disorder: Extending Social Signal Transduction Theory of Depression to account for sex differences in mood disorders. Psychopharmacology, 236(10), 3063–3079. https://doi.org/10.1007/s00213-019-05326-9
Sterley, T. L., Baimoukhametova, D., Füzesi, T., Zurek, A. A., Daviu, N., Rasiah, N. P., Rosenegger, D., & Bains, J. S. (2018). Social transmission and buffering of synaptic changes after stress. Nature neuroscience, 21(3), 393–403. https://doi.org/10.1038/s41593-017-0044-6
Unal, G., & Canbeyli, R. (2019). Psychomotor retardation in depression: A critical measure of the forced swim test. Behavioural Brain Research. https://doi.org/10.1016/j.bbr.2019.112047
Wang, Y. B., Song, N. N., Ding, Y. Q., & Zhang, L. (2022). Neural plasticity and depression treatment. IBRO Neuroscience Reports, 14, 160–184. https://doi.org/10.1016/j.ibneur.2022.09.001
Willner P. (2016). The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiology of stress, 6, 78–93. https://doi.org/10.1016/j.ynstr.2016.08.002
Zeldetz, V., Natanel, D., Boyko, M., Zlotnik, A., Shiyntum, H. N., Grinshpun, J., Frank, D., Kuts, R., Brotfain, E., & Peiser, J. (2018). A new method for inducing a depression-like behavior in rats. Journal of Visualized Experiments, (132), e57137. https://doi.org/10.3791/57137
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Валерія Мізін, Олена Севериновська
This work is licensed under a Creative Commons Attribution 4.0 International License.
