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Castration Eliminates the Impairment Effects of Nandrolone on Passive Avoidance Learning of Adolescent Male Rats

In recent years, the misuse of nandrolone decanoate (ND) among non-athletes, especially adolescent males, has become a growing problem due to the adverse effects of this drug. In our previous study, we have shown that pre-training administration of a high ND dose (100 μg/2.5μl) impairs the acquisition of passive avoidance learning (PAL), but the underlying mechanism has not been clearly evaluated. So, the aim of our study was to evaluate the mechanism of ND effects on the acquisition of PAL in adolescent male rats. Wistar adolescent male rats were divided into 11 groups. Control group received DMSO (2.5μl) + + DMSO (2.5μl), while some experimental groups received ND (100μg/2.5μl), flutamide (5μg/2.5μl), anastrozole (1, 2.5, 5 and 10μg/2.5μl), flutamide (5μg/2.5μl) + ND (100μg/2.5μl), and anastrozole (1μg/2.5μl) + ND (100μg/2.5μl) before training. Rats of groups 10 and 11 were castrated and received i.c.v. 2.5 μl DMSO or 100 μg ND after castration. As was found, administration of 100 μg ND impaired the acquisition of PAL during adolescence, but administration of the androgen receptors blocker and castration could abolish the impairment effects of ND on learning and memory. Therefore, it is suggested that ND affects PAL via activation of androgenic receptors and changing the circulating levels of testosterone.

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References

  1. M. D. Spritzer, M. Gill, A. Weinberg, and L. A. M. Galea, “Castration differentially affects spatial working and reference memory in male rats,” Arch. Sex. Behav., 37, No. 1, 19–29 (2008), https://doi.org/10.1007/s10508-007-9264-2.

    Article  PubMed  Google Scholar 

  2. M. A. Lynch, “Long-term potentiation and memory,” Physiol. Rev., 84, No. 1, 87–136 (2004), https://doi.org/10.1152/physrev.00014.2003.

    CAS  Article  PubMed  Google Scholar 

  3. U. L. W. Rossbach, P. Steensland, F. Nyberg, and P. Le Grevès, “Nandrolone-induced hippocampal phosphorylation of NMDA receptor subunits and ERKs,” Biochem. Biophys. Res. Commun., 357, No. 4, 1028–1033 (2007), https://doi.org/10.1016/j.bbrc.2007.04.037.

    CAS  Article  PubMed  Google Scholar 

  4. C. A. Frye, K. Edinger, and K. Sumida, “Androgen administration to aged male mice increases antianxiety behavior and enhances cognitive performance,” Neuropsychopharmacology, 33, No. 5, 1049–1061 (2008), https://doi.org/10.1038/sj.npp.1301498.

    CAS  Article  PubMed  Google Scholar 

  5. T. Aubele and F. Kritzer, “Androgen influence on prefrontal dopamine systems in adult male rats: localization of cognate intracellular receptors in medial prefrontal projections to the ventral tegmental area and effects of gonadectomy and hormone replacement on glutamate-stimulated extracellular dopamine level,” Cereb. Cortex, 22, No. 8, 1799–1812 (2012), https://doi.org/10.1093/cercor/bhr258.

    CAS  Article  PubMed  Google Scholar 

  6. J. S. Janowsky, S. K. Oviatt, and E. S. Orwoll, “Testosterone influences spatial cognition in older men,” Behav. Neurosci; 108, No. 2, 325–332 (1994), https://doi.org/10.1037//0735-7044.108.2.325.

    CAS  Article  PubMed  Google Scholar 

  7. S. Babanejad, N. Naghdi, and S. A. H. Rohani, “Microinjection of dihydrotestosterone as a 5α-reduced metabolite of testosterone into CA1 region of hippocampus could improve spatial learning in adult male rats,” Iran. J. Pharm. Res., 11, No. 2, 661–669 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Z. Salimi, L. Khajehpour, F. Moradpour, et al., “Nandrolone improves synaptic plasticity at the hippocampus CA1 area and spatial localization in the Morris water maze of male adolescent rats,” Neurosci. Res., 158, 21–29 (2020), https://doi.org/10.1016/j.neures.2019.09.001.

    Article  PubMed  Google Scholar 

  9. P. Rakic, J. P. Bourgeois, and P. S. Goldman-Rakic, “Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness,” Prog. Brain Res., 102, 227–243 (1994), https://doi.org/10.1016/S0079-6123(08)60543-9.

    CAS  Article  PubMed  Google Scholar 

  10. Z. Salimi, A. Pourmotabbed, S. E. Nedaei, et al., “Anastrozole eliminates the improvement effects of nandrolone on hippocampal synaptic plasticity in adolescent male rats,” Biol. Bull., 48, No. 6, 783–792 (2021).

    Article  Google Scholar 

  11. N. J. MacLusky, T. Hajszan, J. Prange-Kiel, and C. Leranth, “Androgen modulation of hippocampal synaptic plasticity,” Neuroscience, 138, No. 3, 957–965 (2006), https://doi.org/10.1016/j.neuroscience.2005.12.054.

    CAS  Article  PubMed  Google Scholar 

  12. S. Basaria, J. T. Wahlstrom, and A. S. Dobs, “Anabolic-androgenic steroid therapy in the treatment of chronic diseases,” J. Clin. Endocrinol. Metab., 86, No. 11, 5108–5117 (2001), https://doi.org/10.1210/jc.86.11.5108.

    CAS  Article  PubMed  Google Scholar 

  13. C. Holland-Hall, “Performance-enhancing substances: is your adolescent patient using it?” Pediatr. Clin. North. Am., 54, No. 4, 651–662 (2007), https://doi.org/10.1016/j.pcl.2007.04.006.

    Article  PubMed  Google Scholar 

  14. D. R. Mottram and A. J. George, “Anabolic steroids,” Baillieres. Best Pract. Res. Clin. Endocrinol. Metab., 14, No. 1, 55–69 (2000), https://doi.org/10.1053/beem.2000.0053.

  15. D. Kouvelas, C. Pourzitaki, G. Papazisis, et al., “Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors,” Int. J. Neuropsychopharmacol., 11, No. 7, 925–934 (2008), https://doi.org/10.1017/S1461145708008754.

    CAS  Article  PubMed  Google Scholar 

  16. K. Magnusson, A. Hanell, I. Bazov, et al., “Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats,” Neurosci. Lett., 467, No. 3, 189–193 (2009), https://doi.org/10.1016/j.neulet.2009.09.041.

    CAS  Article  PubMed  Google Scholar 

  17. A. Zarei, F. Moradpour, A.A. Moazedi, et al., “Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats,” Can. J. Physiol. Pharmacol., 96, No. 2, 130–139 (2018), https://doi.org/10.1139/cjpp-2018-0293.

    CAS  Article  Google Scholar 

  18. J. E. Kerr, R. J. Allore, S. E. Beck, and R. J. Handa, “Distribution and hormonal regulation of androgen receptor (AR) and AR messenger RNA in the rat hippocampus,” Endocrinology, 136, No. 8, 3213–3221 (1995), https://doi.org/10.1210/endo.136.8.7628354.

    CAS  Article  PubMed  Google Scholar 

  19. C. E. Roselli, “The effect of anabolic–androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area,” Brain Res., 792, No. 2, 271–276 (1998), https://doi.org/10.1016/s0006-8993(98)00148-6.

    CAS  Article  PubMed  Google Scholar 

  20. S. Kurling-Kailanto, A. Kankaanpää, J. Hautaniemi, and T. Seppälä, “Blockade of androgen or estrogen receptors reduces nandrolone’s ability to modulate acute reward-related neurochemical effects of amphetamine in rat brain,” Pharmacol. Biochem. Behav., 95, No. 4, 422–427 (2010), https://doi.org/10.1016/j.pbb.2010.02.020.

    CAS  Article  PubMed  Google Scholar 

  21. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, 4th edition, Academic Press, New York, 2002.

    Google Scholar 

  22. D. R. Rubinow and P. J. Schmidt, “Androgens, brain, and behavior,” Am. J. Psychiatry, 153, No. 8, 974–984 (1996), https://doi.org/10.1176/ajp.153.8.974.

    CAS  Article  PubMed  Google Scholar 

  23. Z. Salimi, L. Khajehpour, F. Moradpour, et al., “The study of effect of nilutamide (an androgen receptor antagonist) on spatial learning and memory in adolescent male rats,” J. Arak. Univ. Med. Sci., 22, No. 3, 81–94 (2019).

    Google Scholar 

  24. N. Kokras, N. Pastromas, D. Papasava, et al., “Sex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats,” Psychoneuroendocrinology, 87, 93–107 (2018), https://doi.org/10.1016/j.psyneuen.2017.10.007.

    CAS  Article  PubMed  Google Scholar 

  25. F. Moradpour, N. Naghdi, and Y. Fathollahi, “Anastrozole improved testosterone-induced impairment acquisition of spatial learning and memory in the hippocampal CA1 region in adult male rats,” Behav. Brain Res., 175, No. 2, 223–232 (2006), https://doi.org/10.1016/j.bbr.2006.08.037.

    CAS  Article  PubMed  Google Scholar 

  26. A. I. Svensson, “The aromatase inhibitor1,4,6-androstatriene-3,17-dione (ATD) reduces disinhibitory behavior in intact adult male rats treated with a high dose of testosterone,” Behav. Brain Res., 206, No. 2, 216–222 (2010), https://doi.org/10.1016/j.bbr.2009.09.020.

    CAS  Article  PubMed  Google Scholar 

  27. M. Takahashi, Y. Tatsugi, and T. Kohno, “Endocrinological and pathological effects of anabolic-androgenic steroid in male rats,” Endocr. J., 51, No. 4, 425–434 (2004), https://doi.org/10.1507/endocrj.51.425.

    CAS  Article  PubMed  Google Scholar 

  28. R. Jannatifar, S. Shokri, A. Farrokhi, and R. Nejatbakhsh, “Effect of supraphysiological dose of nandrolone decanoate on the testis and testosterone concentration in mature and immature male rats: A time course study,” Int. J. Reprod. Biomed., 13, No. 12, 779–786 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. S. Purkayastha and R. Mahanta, “Effect of nandrolone decanoate on serum FSH, LH and testosterone concentration in male albino mice,” World J. Life Sci. Med. Res. (Calcutta), 2, No. 3, 123–127 (2012).

    CAS  Google Scholar 

  30. J. McHenry, N. Carrier, E. Hull, and M. Kabbaj, “Sex differences in anxiety and depression, role of testosterone,” Front. Neuroendocrinol., 35, No. 1, 42–57 (2014), https://doi.org/10.1016/j.yfrne.2013.09.001.

    CAS  Article  PubMed  Google Scholar 

  31. V. W. Lee, D. M. de Kretser, B. Hudson, and C. Wang, “Variations in serum FSH, LH and testosterone levels in male rats from birth to sexual maturity,” J. Reprod. Fertil., 42, No. 1, 121–126 (1975), https://doi.org/10.1530/jrf.0.0420121.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to S. E. Nedaei.

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Moradpour, F., Salimi, Z., Zarei, F. et al. Castration Eliminates the Impairment Effects of Nandrolone on Passive Avoidance Learning of Adolescent Male Rats. Neurophysiology 53, 93–100 (2022). https://doi.org/10.1007/s11062-022-09920-0

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  • DOI: https://doi.org/10.1007/s11062-022-09920-0

Keywords

  • adolescence
  • nandrolone
  • learning
  • memory
  • anastrozole
  • flutamide
  • castration