Volume 22, Issue 3 (8-2019)
J Arak Uni Med Sci 2019, 22(3): 81-94 |
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Salimi Z, Khajehpour L, Moradpour F, Moazedi A A, Pourmotabbed A. The Study of Effect of Nilutamide (An Androgen Receptor Antagonist) on Spatial Learning And Memory in Adolescent Male Rats. J Arak Uni Med Sci 2019; 22 (3) :81-94
URL: http://jams.arakmu.ac.ir/article-1-5982-en.html
URL: http://jams.arakmu.ac.ir/article-1-5982-en.html
1- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
2- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran. , khajehpour@scu.ac.ir
3- Fertility & Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4- Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
2- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran. , khajehpour@scu.ac.ir
3- Fertility & Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4- Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract: (2475 Views)
Background and Aim: Nilutamide is a pure non-steroidal antiandrogen that is used in the treatment of advanced-stage (metastatic) prostate cancer and acts as a potent and selective antagonist of the androgen receptors. Previous studies showed that there must be relationship between androgen receptors and cognitive aspects of the brain. Therefore, it seems that nilutamide affects spatial learning and memory through effect on androgen receptors. The aim of this study is to evaluate the effect of nilutamide on spatial localization in the Morris Water Maze and synaptic plasticity at the hippocampus CA1 area of male adolescent rats.
Materials and Methods: In this experimental study, male Wistar rats were randomly divided into 4 groups (n=9). Experimantal groups received vehicle (DMSO 10%) as control groups and different doses of Nilutamide (5, 10 and 15µg/2.5µl). Drug and vehicle were injected for 4 days before training.
Ethical Considerations: This study with research ethics code
EE/ 97, 24, 3061300/ scu.ac.ir has been approved by research ethics committee at Shahid Chamran University of Ahvaz.
Findings: Analysis showed that escape latency and traveled distance for finding hidden platform in the group which received nilutamide (15µg) were significantly lower than of control group at first (p < 0.05) and second (p < 0.01) training days. The results of field potential recording showed that nilutamide had not any significant effect on fEPSP and PS.
Conclusion: The results of peresent study releaved that i.c.v microinjection of nilutamide improved spatial learninig in first and second days, wherease increase of treatment (4 days) not affected spatial learning.
Materials and Methods: In this experimental study, male Wistar rats were randomly divided into 4 groups (n=9). Experimantal groups received vehicle (DMSO 10%) as control groups and different doses of Nilutamide (5, 10 and 15µg/2.5µl). Drug and vehicle were injected for 4 days before training.
Ethical Considerations: This study with research ethics code
EE/ 97, 24, 3061300/ scu.ac.ir has been approved by research ethics committee at Shahid Chamran University of Ahvaz.
Findings: Analysis showed that escape latency and traveled distance for finding hidden platform in the group which received nilutamide (15µg) were significantly lower than of control group at first (p < 0.05) and second (p < 0.01) training days. The results of field potential recording showed that nilutamide had not any significant effect on fEPSP and PS.
Conclusion: The results of peresent study releaved that i.c.v microinjection of nilutamide improved spatial learninig in first and second days, wherease increase of treatment (4 days) not affected spatial learning.
Type of Study: Original Atricle |
Subject:
Basic Sciences
Received: 2019/01/3 | Accepted: 2019/04/17
Received: 2019/01/3 | Accepted: 2019/04/17
References
1. Baudewijntje PC, Gender dysphoria and disorders of sex development: Progress in care and knowledge. Springer Sci & Business Media. pp. 280.
2. Kolvenbag G, Furr B, Blacjledge G,Receptor affinity and potency of non-steroid antiandrogens; translation of preclinical findings into clinical activity, Prostat Cancer and Protatic Diseases. 1998; 1:307-14.
3. Richard C, Medical toxicology. Lippincott William & Wilkins. 2004; pp. 521.
4. Richard A, Pharmocology for nursing care, Elsiver Health Sci. 2013; 1297.
5. Harris MG, Coleman SG, Faulds D, Chrisp P, Nilutamide: A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Prostate Cancer, drugs and aging. 1993; 3(1):2-25.
6. Kerr JE, Allore RJ, Beck SE, Handa RJ,Distribution and hormonal regulation of androgen receptor (AR) and AR messenger RNA in the rat hippocampus, Endocrinol. 1995; 136:3213-21.
7. Choong CS, Wilson EM, Trinucleotide repeats in the human androgen receptor: amolecular basis for disease, J M Endocrinol. 1998; 21:235-57.
8. Kandel E, Schwartz Jh, Jessell Tm. Principles of Neural Science,. Edition F, editor: McGraw-Hill; 2000.
9. Lynch MA, Long-term potentiation and memory, Physiol Rev. 2004;136:84-87.
10. Omar J, The Hippocampal Rate Code: Anatomy, Physiology and Theory. Trends Neurosci. 2009; 32(6):329–38.
11. Hebbard PC, King RR, Malsbury CW, Harley CW, Two organizational effects of pubertal testosterone in male rats: transient social memory and a shift away from long-term potentiation following a tetanus in hippocampal CA1, Exp Neurol. 2003; 182(2): 470-5.
12. Sisk CL, Zehr JL, Pubertal hormones organize the adolescent brain and behavior, Front Neuroendocrinol. 2005; 26:163-74.
13. Martin PD, Berthoz A, Development of spatial firing in the hippocampus of young rats, Hippocampus. 2002; 12(4): 465-80.
14. Scott RC, Richard GR, Holmes GL, Lenck-Santini PP, Maturational dynamics of hippocampal place cells in immature rats, Hippocampus. 2011; 21(4): 347-53.
15. zarei A, moradpour F, moazedi AA, Pourmotabbed A, Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats, Can J Physiol Pharmacol. 2018; 96:1-12.
16. Paxinos C, Watson C. The Rat Brain in Stereotaxic Coordinates 4,. editor. edn. New York: Academic Press. 2002.
17. Pourmotabbed A, Effect of prenatal pentylentetrazol- induced kindling on learning and memory of male offspring, Neurosci. 2011; 172:205-11.
18. Moradpour F, Fathollahi Y, Naghdi N, Hosseinmardi N, Javan M, Prepubertal castration-associated developmental changes in sigma-1 receptor gene expression levels regulate hippocampus area CA1 activity during adolescence, Hippocampus. 2016; 26(7):933–46.
19. Moradpour F, Fathollahi Y, Naghdi N, Hosseinmardi N, Javan M, Prepubertal castration causes the age-dependent changes in hippocampal long-term potentiation, Synapse. 2013; 67:235–44.
20. Tidball P, BurnHV, LunTehK, Volianskis A, CollingridgeGL, FitzjohnSM, Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor–dependent synaptic and intrinsic plasticity, Brain Neurosci Adv. 2017; 1 (1 ):1-24.
21. Naghdi N, Nafisy N, Majlessi N,The effects of intrahippocampal testosterone and flutamide on spatial localization in the Morris water maze., Brain Res. 2001; 897(1-2):44-51.
22. Naghdi N, Oryan S, Etemadi R,The study of spatial memory in adult male rats with injection of testosterone enanthate and flutamide into the basolateral nucleus of the amygdale in Morris water maze. , Brain Res 2003; 972:1-8.
23. Kouvelas D, Pourzitaki C, Papazisis G, Dagklis T, Dimou K, Kraus MM,Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors, int j neuropsychopharmacol. 2008; 11(7): 925-34.
24. Barrett-Connor E, Edelstein SL, A prospective study of dehydroepiandrosterone sulfate and cognitive function in an older population: the Rancho Bernardo Study, J Am Geriatr Soc. 1994; 42(4): 420-3.
25. Hampson E, Estrogen-related variations in human spatial and articulatory-motor skills, Psychoneuroendocrinol.1990; 15(2): 97-111.
26. Voyer D, Voyer S, Bryden MP, Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables, Psychol Bull. 1995; 117(2): 250-70.
27. Vallee M, Mayo W, Koob GF, Le Moal M, Neurosteroids in learning and memory processes, Int Rev Neurobiol. 2001; 46:273-320.
28. J afari-Sabet M, NMDA receptor blockers prevents the facilitatory effects of post-training intra-dorsal hippocampal NMDA and physostigmine on memory retention of passive avoidance learning in rats, Behav Brain Res. 2006; 169(1):120-7.
29. Kimoto T, Tsurugizawa T, Ohta Y, Makino J, Tamura H, Hojo Y, Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-Daspartate and calcium-dependent synthesis, Endocrinol. 2001; 142(8):3578-89.
30. Migues PV, Johnston ANB, Rose SPR, Dehydroepiandrosterone and its sulfate enhance memory retention in day-old chicks, Neurosci .2002; 109: 243-51.
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