Skip to main content
SpringerLink
Log in

Anastrozole Eliminates the Improvement Effects of Nandrolone on Hippocampal Synaptic Plasticity in Adolescent Male Rats

  • ANIMAL AND HUMAN PHYSIOLOGY
  • Published:
Biology Bulletin Aims and scope Submit manuscript

Abstract

Background: Nandrolone Decanoate (ND) is one of the most popular androgenic anabolic steroids (AASs) compounds that is widely abused during adolescence. Despite clear evidence about the effects of ND on hippocampal synaptic plasticity, its complex underlying mechanisms of action have remained elusive. Therefore, the aim of this study is to evaluate the role of P450 aromatase in the mediation of ND effects on hippocampal CA1 synaptic plasticity during adolescence in male rats. Material and Methods: In the present study, the rats were divided into four groups: Control group received DMSO, while other experimental groups received ND (60 µg/2.5 µL), anastrozole (1 µg/2.5 µL), and co-adminstration of anastrozole (1 µg/2.5 µL) and ND (60 µg/2.5 µL) for 4 days. Then, Field excitatory postsynaptic potential (fEPSP) and Population spikes (PS) magnitudes were investigated in the hippocampal CA1 area. Results: Electrophysiological results indicated higher fEPSP-LTP magnitude in the ND-treated group compared to DMSO-treated group (P < 0.05). Also, the results of field potential recording showed that anastrozole alone had not a significant effect on fEPSP-LTP magnitude, while pre-administration of anastrozole abolished the ND improvement effects on fEPSP-LTP magnitude. Conclusion: This study presented evidence supporting the involvement of aromatase in improvement effects of ND on hippocampal synaptic plasticity in adolescent male rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

REFERENCES

  1. Abel, T., Lattal, K.M., Molecular mechanisms of memory acquisition, consolidation and retrieval, Curr Opin Neurobiol., 2001, vol. 11, no. 2, pp. 180–187.

    Article  CAS  Google Scholar 

  2. Basaria, S.W. and Dobs, A.S., Anabolic-androgenic steroid therapy in the treatment of chronic diseases, Clin Endocrinol. Metab., 2001, vol. 86, pp. 5108–5117.

    Article  CAS  Google Scholar 

  3. Beltran-Campos, V., Prado-Alcala, R.A., Leon-Jacinto, U., Aguilar-Vazquez, A., Quirarte, G.L., Ramirez-Amaya, V., and Diaz-Cintra, S., Increase of mushroom spine density in CA1 apical dendrites produced by water maze training is prevented by ovariectomy, Brain Res., 2011, vol. 1369, pp. 119–130.

    Article  CAS  Google Scholar 

  4. Bliss, T.V. and Collingridge, G.L., A synaptic model of memory: long-term potentiation in the hippocampus, Nature, 19936, vol. 361, no. 6407, pp. 31–39.

  5. Cunningham, R.L., Claiborne, B.J, and McGinnis, M.Y., Pubertal exposure to anabolic androgenic steroids increases spine densities on neurons in the limbic system of male rats., Neuroscience, 2007, vol. 150, pp. 609–615.

    Article  CAS  Google Scholar 

  6. Foy, M.R., Xu, J., Xie, X., Brinton, R.D., Thompson, R.F., and Berger, T.W.,17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation, J. Neurophysiol., 1999, vol. 81, pp. 925–929.

    Article  CAS  Google Scholar 

  7. Grassi, S., Frondaroli, A., Scarduzio, M., Dutia, M.B., Dieni, C., and Pettorossi, V.E., Effects of 17-estradiol on glutamate synaptic transmission and neuronal excitability in the rat medial vestibular nuclei, Neuroscience, 2011, vol. 165, pp. 1100–1114.

    Article  Google Scholar 

  8. Holland-Hall, C., Performance-enhancing substances: is your adolescent patient using?, Pediatr. Clin. North Am., 2007, vol. 54, pp. 651–662.

    Article  Google Scholar 

  9. Kokras, N., Pastromas, N., Papasava, D., de Bournonville, C., Cornil, C.A., and Dalla, C., Sex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats, Psychoneuroendocrinology, 2018, vol. 87, pp. 93–107.

    Article  CAS  Google Scholar 

  10. Liisa, A.M., Tiffany, T.Y.A., and Alasdair, M., High level of estradiol impair spatial performance in the Morris water maze and increase “depressive-like” behaviors in the female meadow vole, Physiol. Behav., 2002, vol. 77, pp. 217–225.

    Article  Google Scholar 

  11. Lynch, M.A., Long-term potentiation and memory, Physiol. Rev., 2004, vol. 84, pp. 87–136.

    Article  CAS  Google Scholar 

  12. MacLusky, N.J., Hajszan, T., Prange-Kiel, J., and Leranth, C., Androgen modulation of hippocampal synaptic plasticity, Neuroscience, 2006, vol. 138, pp. 957–965.

    Article  CAS  Google Scholar 

  13. Magnusson, K., Bazov, I., Clausen, F., and Zhou, Q., Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats, Neurosci. Lett., 2009, vol. 46, pp. 189–193.

    Article  Google Scholar 

  14. McAllister, M., Anabolic-androgenic steroid abuse by physicians, J Addict Dis., 2006, vol. 25, pp. 105–110.

    Article  Google Scholar 

  15. Mohammadi-Farani, A., Haghighi, A., and Ghazvineh, M., Effects of long term administration of testosterone and estradiol on spatial memory in rats, Res. Pharm. Sci., 2015, vol. 10, pp. 407–418.

    PubMed  PubMed Central  Google Scholar 

  16. Moradpour, F., Fathollahi, Y., Naghdi, N., Hosseinmardi, N., and Javan, M., Prepubertal castration causes the age-dependent changes in hippocampal long-term potentiation, Synapse, 2013, vol. 67, pp. 235–244.

    Article  CAS  Google Scholar 

  17. Moradpour, F., Naghdi, N., and Fathollahi, Y., Anastrozole improved testosterone-induced impairment acquisition of spatial learning and memory in the hippocampal CA1 region in adult male rats, Behav. Brain Res., 2006, vol. 175, pp. 223–232.

    Article  CAS  Google Scholar 

  18. Mottram, D.R. and George, A.J., Anabolic steroids, Baillieres Best Pract. Res. Clin. Endocrinol. Metab., 2000, vol. 14, no. 1, pp. 55–69.

    Article  CAS  Google Scholar 

  19. Naftolin, F. and Maclusky, N.J., Aromatization hypothesis revisited, in Sexual Differentiation: Basic and Clinical Aspects, Serio, M., Motta, M., Zanisi, M., and Martini, L., Eds., New York: Raven Press, 1984, pp. 79–91.

    Google Scholar 

  20. Naghdi, N. and Asadollahi, A., Genomic and nongenomic effects of intrahippocampal microinjection of testosterone on long-term memory in male adult rats, Behav. Brain Res., 2004, vol. 153, pp. 1–6.

    Article  CAS  Google Scholar 

  21. Paxinos, C. and Watson, C., The Rat Brain in Stereotaxic Coordinates 4, Editor. Ed., New York: Academic, 2002.

  22. Rakic, P., Bourgeois, J.P., and Goldman-Rakic, P.S., Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness, Prog. Brain Res., 1994, vol. 102, pp. 227–243.

    Article  CAS  Google Scholar 

  23. Roselli, C.E., The effect of anabolic–androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area, Brain Res., 1998, vol. 792, pp. 271–276.

    Article  CAS  Google Scholar 

  24. Rudick, C.N., Woolley, C.S., Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in the adult female rat, J. Neurosci., 2001, vol. 21, pp. 6532–6543.

    Article  CAS  Google Scholar 

  25. Ryan, K.J., Biological aromatization of steroids, J. Biol. Chem., 1959, vol. 234, pp. 268–272.

    Article  CAS  Google Scholar 

  26. Salimi, Z., Khajehpour, L., Moradpour, F., Moazedi, A.A., Pourmotabbed, A., and Zarei, F., Nandrolone improve synaptic plasticity at the hippocampus CA1 area and spatial localization in the Morris water maze of male adolescent rats, Neurosci. Res., 2020, vol. 158, pp. 21–29.

    Article  Google Scholar 

  27. Salimi, Z., Moradpour, F., Zarei, F., Rashidi, Z., Khazaei, M.H., and Ahmadi, S.M., The effect of blockade of androgen receptors by flutamide on learning and memory, synaptic plasticity and behavioral performances: a review study, Cell Tissue Biol., 2021, vol. 15, no. 4, pp. 337–346.

    Article  Google Scholar 

  28. Salimi, Z., Moradpour, F., Khajehpour, L., Moazedi, A.A., and Pourmotabbed, A. The role of aromatase and castration on spatial learning and memory changes by nandrolone, Avicenna J. Neuro Psycho Physiol., 2017, vol. 4, no. 4, pp. 153–162.

    Google Scholar 

  29. Schanzer, W., Metabolism of anabolic androgenic steroids, Clin Chem., 1996, vol. 42, no. 7, pp. 1001–1020.

    Article  CAS  Google Scholar 

  30. Schleich, C.E., Ontogeny of spatial working memory in the subterranean rodent ctenomys talarum, Dev. Psychobiol., 2010, vol. 52, pp. 592–597.

    Article  Google Scholar 

  31. Severi, S., Guidi, S., Ciani, E.E., Bartesaghi, R., Sex differences in the stereological parameters of the hippocampal dentate gyrus of the guinea-pig before puberty, Neuroscience, 2005, vol. 132, pp. 375–386.

    Article  CAS  Google Scholar 

  32. Smith, C.C. and McMahon. L.L., Estrogen-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors, J. Neurosci., 2006, vol. 26, pp. 8517–8522.

    Article  CAS  Google Scholar 

  33. Smith, C.C., Vedder, .LC., Nelson, A.R., Bredemann, T.M., and McMahon, L.L., Duration of estrogen deprivation, not chronological age, prevents estrogen’s ability to enhance hippocampal synaptic physiology, Proc. Natl. Acad. Sci. U. S. A., 2010, vol. 107, pp. 19543–19548.

    Article  CAS  Google Scholar 

  34. Spear, L.P., The adolescent brain and age-related behavioral manifestations, Neurosci. Biobehav. Rev., 2000, vol. 24, pp. 417–463.

    Article  CAS  Google Scholar 

  35. Su, J., Sripanidkulchai, B., Sripanidkulchai, K., Piyachaturawat, P., and Wara-Aswapati, N., Effect of Curcuma comosa and estradiol on the spatial memory and hippocampal estrogen receptor in the post-training ovariectomized rats, J. Nat. Med., 2011, vol. 65, pp. 57–62.

    Article  Google Scholar 

  36. Svensson, A.I., The aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) reduces disinhibitory behavior in intact adult male rats treated with a high dose of testosterone, Behav Brain Res., 2010, vol. 2, pp. 216–222.

    Article  Google Scholar 

  37. Tabori, N.E., Stewart, L.S., Znamensky, F., Romeo, R.D., Alves, S.E., Mcewen, B.S., and Milner, T.A., Ultrastructural evidence that androgen receptors are located at extranuclear sites in the rat hippocampal formation, Neuroscience, 2005, vol. 130, pp. 151–163.

    Article  CAS  Google Scholar 

  38. Willard, S.S. and Koochekpour, S., Glutamate, glutamate receptors, and downstream signaling pathways, Int. J. Biol. Sci., 2013, vol. 9, no. 9, pp. 948–959.

    Article  CAS  Google Scholar 

  39. Wu, W.W., Adelman, J.P., and Maylie. J., Ovarian hormone deficiency reduces intrinsic excitability and abolishes acute estrogen sensi tivity in hippocampal CA1 pyramidal neurons, J. Neurosci., 2011, vol. 31, pp. 2638–2648.

    Article  CAS  Google Scholar 

Download references

Funding

We gratefully acknowledge Kermanshah University of Medical Sciences for supporting this study.

Author information

Authors and Affiliations

  1. Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Zahra Salimi, Ali Pourmotabbed, Seyed Ershad Nedaei, Farshad Moradpour & Fatemeh Zarei

  2. Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Zahra Salimi, Mohammad Rasool Khazaei, Farshad Moradpour & Fatemeh Zarei

  3. Department of Biology, Centre for Biomedical Research, University of Victoria, Victoria, BC V8P 5C2, Canada

    Farshad Moradpour

Authors
  1. Zahra Salimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Pourmotabbed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seyed Ershad Nedaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Rasool Khazaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farshad Moradpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fatemeh Zarei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Farshad Moradpour or Fatemeh Zarei.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international guidelines for the care and use of animals were followed. All procedures were approved by the local Animal Ethics Committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zahra Salimi, Pourmotabbed, A., Nedaei, S.E. et al. Anastrozole Eliminates the Improvement Effects of Nandrolone on Hippocampal Synaptic Plasticity in Adolescent Male Rats. Biol Bull Russ Acad Sci 48, 783–792 (2021). https://doi.org/10.1134/S1062359021130070

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062359021130070

Keywords:

Search

Navigation