Nandrolone decanoate reduces the positive effects of resistance training on cognition, anxious behavior, and hippocampal morphology in rats

Authors

DOI:

https://doi.org/10.33448/rsd-v11i8.30600

Keywords:

Memory; Exercise; Testosterone; Hypertrofhy; Behavior.

Abstract

AAs became popular among competitive athletes and the general population for recreational and performance purposes. The indiscriminate use of AAs occurs in supraphysiological doses and negatively affects cognition.   Moreover, nandrolone decanoate (DECA) abuse may reduce the beneficial effects of resistance training (RT) on health. Objective: We aimed to investigate if DECA administration in supraphysiological doses interferes with the positive effects of RT on anxious behavior, memory, and morphology of neurons in the hippocampus of rats. Materials and Methods: Rats were randomly assigned into four groups (N= 12): Control (C); DECA (D); Trained (T) Trained+DECA (TD). EAA DECA was administered in daily supraphysiological doses of 15mg/kg during the 8 weeks of the RT protocol. All groups performed a maximum load test before and after the RT protocol; anxious behavior and memory tests were performed, and thereafter, rats were euthanized for morphologic analyses of the hippocampus.  DECA produced an anxiogenic effect, worsened cognition and reduced the thickness of the grainy layer of the DG in the hippocampus. Moreover, DECA reduced the positive effects of RT on cognition and DG neurons. This is the first study showing that suprapharmacological doses of DECA reduce the positive effects of RT on memory and the thickness of the granular layer of the DG.

References

Ambar, G., & Chiavegatto, S. (2009). Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice. Genes, Brain and Behavior, 8(2), 161–173. https://doi.org/10.1111/j.1601-183X.2008.00458.x

Bhasin, S. (2000). Testosterone Replacement and Resistance Exercise in HIV-Infected Men With Weight Loss and Low Testosterone Levels. JAMA, 283(6), 763. https://doi.org/10.1001/jama.283.6.763

Bhasin, S., Hatfield, D. L., Hoffman, J. R., Kraemer, W. J., Labotz, M., Phillips, S. M., & Ratamess, N. A. (2021). Anabolic-Androgenic Steroid Use in Sports, Health, and Society. Medicine & Science in Sports & Exercise, 53(8), 1778–1794. https://doi.org/10.1249/MSS.0000000000002670

Bhasin, S., Storer, T. W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., Bunnell, T. J., Tricker, R., Shirazi, A., & Casaburi, R. (1996). The Effects of Supraphysiologic Doses of Testosterone on Muscle Size and Strength in Normal Men. New England Journal of Medicine, 335(1), 1–7. https://doi.org/10.1056/NEJM199607043350101

Bompa, T. O., & Haff, G. G. (2012). Periodização Teoria e Metodologia do Treinamento (Phorte (ed.); 5a). Phorte.

Bourin, M., Petit-Demoulière, B., Nic Dhonnchadha, B., & Hascöet, M. (2007). Animal models of anxiety in mice. Fundamental & Clinical Pharmacology, 21(6), 567–574. https://doi.org/10.1111/j.1472-8206.2007.00526.x

Camarda, S. R. de A., Tebexreni, A. S., Páfaro, C. N., Sasai, F. B., Tambeiro, V. L., Juliano, Y., Barros Neto, T. L. de, Edwards, L. J., Nelson, M. E., Rejeski, W. J., Blair, S. N., Duncan, P. W., Judge, J. O., King, A. C., MacEra, C. A., Castaneda-Sceppa, C., Bos, I., De Boever, P., Int Panis, L., … De Mello, M. T. (2012). Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience, 44(2), 1–7. https://doi.org/10.1016/j.neuroscience.2011.11.029

Camiletti-Moirón, D., Aparicio, V. A., Nebot, E., Medina, G., Martínez, R., Kapravelou, G., Andrade, A., Porres, J. M., López-Jurado, M., & Aranda, P. (2015). High-intensity Exercise Modifies the Effects of Stanozolol on Brain Oxidative Stress in Rats. Int J Sports Med, 36(12), 984–991. https://doi.org/DOI: 10.1055 / s-0035-1548941

Cassilhas, R. C., Lee, K. S., Fernandes, J. C. J., Oliveira, M. G. M., Tufik, S. S., Meeusen, R., Mello, M. T. De, Gomes, F. C. F. G. N., Fernandes, J. C. J., Campos, D. V., Cassilhas, R. C., Viana, G. M., D’Almeida, V., de Moraes Rêgo, M. K., Buainain, P. I., Cavalheiro, E. A., Arida, R. M., Viana, V. A. R., Grassmann, V., … Delacour, J. (2020). The impact of resistance exercise on the cognitive function of the elderly. Medicine and Science in Sports and Exercise, 39(1), 1–9. https://doi.org/10.1249/mss.0b013e318060111f

Cassilhas, R. C., Lee, K. S., Fernandes, J., Oliveira, M. G. M., Tufik, S., Meeusen, R., & De Mello, M. T. (2012). Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience. https://doi.org/10.1016/j.neuroscience.2011.11.029

Cassilhas, R. C., Lee, K. S., Venâncio, D. P., Oliveira, M. G. M., Tufk, S., & de Mello, M. T. (2012). Resistance exercise improves hippocampus-dependent memory. Brazilian Journal of Medical and Biological Research. https://doi.org/10.1590/S0100-879X2012007500138

Cassilhas, R. C., Reis, I. T., Venâncio, D., Fernandes, J., Tufik, S., & Mello, M. T. de. (2013). Animal model for progressive resistance exercise: a detailed description of model and its implications for basic research in exercise. Motriz: Revista de Educação Física, 19(1), 178–184. https://doi.org/10.1590/S1980-65742013000100018

Cassilhas, R. C., Tufik, S., & Mello, M. T. de. (2016). Physical exercise, neuroplasticity, spatial learning and memory Ricardo. International Journal of Powder Metallurgy, 53(1), 27–36. https://doi.org/10.1007/s00018-015-2102-0

Cassilhas, R. C., Viana, V. A. R., Grassmann, V., Santos, R. T., Santos, R. F., Tufik, S., & Mello, M. T. (2007). The impact of resistance exercise on the cognitive function of the elderly. Medicine and Science in Sports and Exercise, 39(8), 1401–1407. https://doi.org/10.1249/mss.0b013e318060111f

Chen, C., Nakagawa, S., An, Y., Ito, K., Kitaichi, Y., & Kusumi, I. (2017). The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels. Frontiers in Neuroendocrinology, 44, 83–102. https://doi.org/10.1016/j.yfrne.2016.12.001

Costine, B. A., Oberlander, J. G., Davis, M. C., Penatti, C. A. A., Porter, D. M., Leaton, R. N., & Henderson, L. P. (2010). Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse. Psychoneuroendocrinology, 35(10), 1473–1485. https://doi.org/10.1016/j.psyneuen.2010.04.015

De Sousa, R. A. L. (2018). Brief report of the effects of the aerobic, resistance, and high-intensity interval training in type 2 diabetes mellitus individuals. International Journal of Diabetes in Developing Countries, 38(2), 138–145. https://doi.org/10.1007/s13410-017-0582-1

De Sousa, R. A. L., Caria, A. C. I., De Jesus Silva, F. M., Diniz e Magalhães, C. O., Freitas, D. A., Lacerda, A. C. R., Mendonça, V. A., Cassilhas, R. C., & Leite, H. R. (2020). High-intensity resistance training induces changes in cognitive function, but not in locomotor activity or anxious behavior in rats induced to type 2 diabetes. Physiology & Behavior, 223(June), 1–7. https://doi.org/10.1016/j.physbeh.2020.112998

de Sousa, R. A. L., de Lima, E. V., da Silva, T. P., de Souza, R. V., Figueiredo, C. P., Passos, G. F., & Clarke, J. R. (2019). Late Cognitive Consequences of Gestational Diabetes to the Offspring, in a New Mouse Model. Molecular Neurobiology, 56(11), 7754–7764. https://doi.org/10.1007/s12035-019-1624-0

De Sousa, R. A. L., Rocha-Dias, I., de Oliveira, L. R. S., Improta-Caria, A. C., Monteiro-Junior, R. S., & Cassilhas, R. C. (2021). Molecular mechanisms of physical exercise on depression in the elderly: a systematic review. Molecular Biology Reports, 48(4), 3853–3862. https://doi.org/10.1007/s11033-021-06330-z

Devanne, H., & Allart, E. (2019). Boosting brain motor plasticity with physical exercise. Neurophysiologie Clinique, 2018, 2018–2020. https://doi.org/10.1016/j.neucli.2019.01.003

Egan, B., & Zierath, J. R. (2013). Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation. Cell Metabolism, 17(2), 162–184. https://doi.org/10.1016/j.cmet.2012.12.012

Figueiredo, C. P., Clarke, J. R., Ledo, J. H., Ribeiro, F. C., Costa, C. V., Melo, H. M., Mota-Sales, A. P., Saraiva, L. M., Klein, W. L., Sebollela, A., De Felice, F. G., & Ferreira, S. T. (2013). Memantine Rescues Transient Cognitive Impairment Caused by High-Molecular-Weight A Oligomers But Not the Persistent Impairment Induced by Low-Molecular-Weight Oligomers. Journal of Neuroscience, 33(23), 9626–9634. https://doi.org/10.1523/JNEUROSCI.0482-13.2013

Fleck, S. J., & Kraemer, W. J. (2017). Fundamentos do treinamento de força muscular. In Fundamentos do treinamento de força muscular [recurso eletrônico] / Steven J. Fleck, William J. Kraemer ; tradução: Jerri Luis Ribeiro, Regina Machado Garcez ; revisão técnica: Ronei Silveira Pinto, Matheus Daros Pinto. – 4. ed. – Porto Alegre : Artmed, 2.

Gomez-Pinilla, F., & Hillman, C. (2013). The Influence of Exercise on Cognitive Abilities - Comprehensive Physiology. https://doi.org/10.1002/cphy.c110063.The

Greising, S. M., Gransee, H. M., Mantilla, C. B., & Sieck, G. C. (2012). Systems biology of skeletal muscle: fiber type as an organizing principle. WIREs Systems Biology and Medicine, 4(5), 457–473. https://doi.org/10.1002/wsbm.1184

Hartgens, F., & Kuipers, H. (2004). Effects of androgenic-anabolic steroids in athletes. Sports Medicine, 34(8), 513–554. https://doi.org/10.2165/00007256-200434080-00003

Hayek, L. El, Khalifeh, M., Zibara, V., Assaad, R. A., Emmanuel, N., El-ghandour, R., Nasrallah, P., Bilen, M., Ibrahim, P., Younes, J., Haidar, A., Barmo, N., Jabre, V., Stephan, J. S., Sleiman, S. F., Emmanuel, N., Karnib, N., El-ghandour, R., Nasrallah, P., … Sleiman, S. F. (2019). Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor ( BDNF ). https://doi.org/10.1523/JNEUROSCI.1661-18.2019

Joksimovic, J., Selakovic, D., Jovicic, N., Mitrovic, S., Mihailovic, V., Katanic, J., Milovanovic, D., & Rosic, G. (2019). Exercise Attenuates Anabolic Steroids-Induced Anxiety via Hippocampal NPY and MC4 Receptor in Rats. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00172

Joksimovic, J., Selakovic, D., Matovic, M., Zaletel, I., Puskas, N., & Rosic, G. (2017). The role of neuropeptide-Y in nandrolone decanoate-induced attenuation of antidepressant effect of exercise. PLOS ONE, 12(6), e0178922. https://doi.org/10.1371/journal.pone.0178922

Joukar, S., Vahidi, R., Farsinejad, A., Asadi-shekaari, M., & Shahouzehi, B. (2017). Ameliorative Effects of Endurance Exercise with Two Different Intensities on Nandrolone Decanoate-Induced Neurodegeneration in Rats: Involving Redox and Apoptotic Systems. Neurotoxicity Research, 32(1), 41–49. https://doi.org/10.1007/s12640-017-9705-1

Kanayama, G., Hudson, J. I., & Jr, H. G. P. (2009). Long Term Psychiatric and Medical Consequences of Anabolic Androgenic Steroid Abuse. Drug and Alcohol Dependence, 98(617), 1–12. https://doi.org/10.1016/j.drugalcdep.2008.05.004.Long-Term

Kanayama, G., & Pope, H. G. (2018). History and epidemiology of anabolic androgens in athletes and non-athletes. Molecular and Cellular Endocrinology, 464, 4–13. https://doi.org/10.1016/j.mce.2017.02.039

Kumar, V., Bhat, Z. A., & Kumar, D. (2013). Animal models of anxiety: A comprehensive review. Journal of Pharmacological and Toxicological Methods, 68(2), 175–183. https://doi.org/10.1016/j.vascn.2013.05.003

Kutscher, E. C., Lund, B. C., & Perry, P. J. (2002). A Review for the Clinician. Sports Med, 32(5), 285–296.

Lefaucheur, J. P. (2019). Boosting physical exercise with cortical stimulation or brain doping using tDCS: Fact or myth? Neurophysiologie Clinique, 2018, 20–23. https://doi.org/10.1016/j.neucli.2019.01.002

Lista, I., & Sorrentino, G. (2010). Biological mechanisms of physical activity in preventing cognitive decline. In Cellular and Molecular Neurobiology (Vol. 30, Issue 4, pp. 493–503). https://doi.org/10.1007/s10571-009-9488-x

Mariotti, R., Fattoretti, P., Malatesta, M., Nicolato, E., Sandri, M., & Zancanaro, C. (2014). Forced mild physical training improves blood volume in the motor and hippocampal cortex of old mice. The Journal of Nutrition, Health & Aging, 18(2), 178–183. https://doi.org/10.1007/s12603-013-0384-1

McCall, G. E., Byrnes, W. C., Dickinson, A., Pattany, P. M., & Fleck, S. J. (1996). Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. Journal of Applied Physiology, 81(5), 2004–2012. https://doi.org/10.1152/jappl.1996.81.5.2004

Nieschlag, E., & Nieschlag, S. (2019). The history of discovery , synthesis and development of testosterone for clinical use. European Society of Endocrinology, 180(6), 201–212.

Novaes Gomes, F. G., Fernandes, J., Vannucci Campos, D., Cassilhas, R. C., Viana, G. M., D’Almeida, V., de Moraes Rêgo, M. K., Buainain, P. I., Cavalheiro, E. A., & Arida, R. M. (2014). The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2014.08.009

Oberlander, J. G., & Henderson, L. P. (2012). Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse. Neuropsychopharmacology, 37(6), 1483–1499. https://doi.org/10.1038/npp.2011.334

Pagonis, T. A., Angelopoulos, N. V., Koukoulis, G. N., & Hadjichristodoulou, C. S. (2006). Psychiatric side effects induced by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse. European Psychiatry, 21(8), 551–562. https://doi.org/10.1016/j.eurpsy.2005.09.001

Parkinson, A. B., & Evans, N. A. (2006). Anabolic Androgenic Steroids: A Survey of 500 Users. Medicine & Science in Sports & Exercise, 38(4). https://journals.lww.com/acsm-msse/Fulltext/2006/04000/Anabolic_Androgenic_Steroids__A_Survey_of_500.6.aspx

Paxinos, G., & Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates (I. Academic Press (ed.); 6th ed.).

Pope, H. G., Gruber, A. J., Choi, P., Olivardia, R., & Phillips, K. A. (1997). Muscle Dysmorphia: An Underrecognized Form of Body Dysmorphic Disorder. Psychosomatics, 38(6), 548–557. https://doi.org/10.1016/S0033-3182(97)71400-2

Pope, H. G., Gruber, A. J., Mangweth, B., Bureau, B., DeCol, C., Jouvent, R., & Hudson, J. I. (2000). Body Image Perception Among Men in Three Countries. American Journal of Psychiatry, 157(8), 1297–1301. https://doi.org/10.1176/appi.ajp.157.8.1297

Pope, H. G., Kanayama, G., Athey, A., Ryan, E., Hudson, J. I., & Baggish, A. (2014). The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: Current best estimates. The American Journal on Addictions, 23(4), 371–377. https://doi.org/10.1111/j.1521-0391.2013.12118.x

Pope JR, H. G., Katz, D. L., & Hudson, J. I. (1993). Anorexia nervosa and “reverse anorexia” among 108 male bodybuilders. Comprehensive Psychiatry, 34(6), 406–409. https://doi.org/https://doi.org/10.1016/0010-440X(93)90066-D

Selakovic, D., Joksimovic, J., Zaletel, I., Puskas, N., Matovic, M., & Rosic, G. (2017). The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin–positive interneurons. PLOS ONE, 12(12), e0189595. https://doi.org/10.1371/journal.pone.0189595

Seo, D. Y., Lee, S. R., Kim, N., Ko, K. S., Rhee, B. D., & Han, J. (2014). Humanized animal exercise model for clinical implication. Pflugers Archiv European Journal of Physiology, 466(9), 1673–1687. https://doi.org/10.1007/s00424-014-1496-0

Su, T. P., Pagliaro, M., Schmidt, P. J., Pickar, D., Wolkowitz, O., & Rubinow, D. R. (1993). Neuropsychiatric effects of anabolic steroids in male normal volunteers. JAMA, 269(21), 2760–2764. http://www.ncbi.nlm.nih.gov/pubmed/8492402

Tanehkar, F., Rashidy-Pour, A., Vafaei, A. A., Sameni, H. R., Haghighi, S., Miladi-Gorji, H., Motamedi, F., Akhavan, M. M., & Bavarsad, K. (2013). Voluntary exercise does not ameliorate spatial learning and memory deficits induced by chronic administration of nandrolone decanoate in rats. Hormones and Behavior, 63(1), 158–165. https://doi.org/10.1016/j.yhbeh.2012.10.003

Tsametis, C. P., & Isidori, A. M. (2018). Testosterone replacement therapy: For whom, when and how? Metabolism, 86, 69–78. https://doi.org/10.1016/j.metabol.2018.03.007

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11/06/2022

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MAGALHÃES, C. O. D. e; OLIVEIRA, L. R. S. de; SANTOS, S. T. .; MENDES, B. F. .; DIAS, I. R. .; CRUZ , P. P. .; SAMPAIO, K. H. .; PEIXOTO, M. F. D. .; SOUSA, R. A. L. de .; CASSILHAS, R. C. Nandrolone decanoate reduces the positive effects of resistance training on cognition, anxious behavior, and hippocampal morphology in rats. Research, Society and Development, [S. l.], v. 11, n. 8, p. e10511830600, 2022. DOI: 10.33448/rsd-v11i8.30600. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/30600. Acesso em: 26 apr. 2024.

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Health Sciences