Volume 9, Issue 1 (January & February 2018 2018)                   BCN 2018, 9(1): 5-14 | Back to browse issues page


XML Print


1- Department of Toxicology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:  

Introduction: Scopolamine, a muscarinic cholinergic receptor antagonist, is widely used to induce memory impairment in experimental animals. The present study aims to compare memory impairment and oxidative stress following single and repeated doses administration of scopolamine.
Methods: A group of rats received a single shot of scopolamine in different doses (0.5, 1, or 3 mg/kg, IP) 24 hours after the passive avoidance training. Then the memory retrieval test was performed 30 minutes and 7 days after the injection. In the other experiment, rats received similar doses of scopolamine for 7 consecutive days, 24 hours after the training session. Then the memory retrieval test was performed 30 minutes and 7 days after the last injection. Acetylcholinesterase (AChE) activity and lipid peroxidation were measured in their hippocampus tissue, too.
Results: Scopolamine administered in repeated doses caused more impairment in memory function compared to single dose injection based on the evaluation 30 minutes after injection. Moreover, the memory impairment persisted for 7 days only in repeated doses treated groups. Increase in acetylcholinesterase activity and lipid peroxidation in both groups was observed 30 minutes after scopolamine administration. These abnormal increases persisted for 7 days only in repeated doses treated groups. Increased AChE activity and lipid peroxidation was well correlated with behavioral deficit. Also AChE activity was well associated with lipid peroxidation. 
Conclusion: The results of present study showed that repeated administration of scopolamine induced results in memory impairment. This effect can be due to long-lasting oxidative stress which may damage the hippocampus tissue. 

Type of Study: Original | Subject: Behavioral Neuroscience
Received: 2016/05/2 | Accepted: 2017/02/25 | Published: 2018/01/1

References
1. Aalto, S. (2005). Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: A positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457. Journal of Neuroscience, 25(10), 2471–7. doi: 10.1523/jneurosci.2097-04.2005 [DOI:10.1523/JNEUROSCI.2097-04.2005]
2. Abd-El-Fattah, M. A., Abdelakader, N. F., & Zaki, H. F. (2014). Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive impairment in rats. European Journal of Pharmacology, 723, 330–8. doi: 10.1016/j.ejphar.2013.11.008 [DOI:10.1016/j.ejphar.2013.11.008]
3. Ahmad, A., Ramasamy, K., Jaafar, S. M., Majeed, A. B. A., & Mani, V. (2014). Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain. Food and Chemical Toxicology, 65, 120–8. doi: 10.1016/j.fct.2013.12.025 [DOI:10.1016/j.fct.2013.12.025]
4. Akiyama, H., Arai, T., Kondo, H., Tanno, E., Haga, C., & Ikeda, K. (2000). Cell mediators of inflammation in the alzheimer disease brain. Alzheimer Disease and Associated Disorders, 14(Supplement), S47–S53. doi: 10.1097/00002093-200000001-00008 [DOI:10.1097/00002093-200000001-00008]
5. Azami, N. S., Piri, M., Oryan, S., Jahanshahi, M., Babapour, V., & Zarrindast, M. R. (2010). Involvement of dorsal hippocampal α-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task. Neurobiology of Learning and Memory, 93(4), 455–62. doi: 10.1016/j.nlm.2010.01.003 [DOI:10.1016/j.nlm.2010.01.003]
6. Barnes, N. M., & Sharp, T. (1999). A review of central 5-HT receptors and their function. Neuropharmacology, 38(8), 1083–152. doi: 10.1016/s0028-3908(99)00010-6 [DOI:10.1016/S0028-3908(99)00010-6]
7. Bradford, M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248–54. doi: 10.1006/abio.1976.9999 [DOI:10.1006/abio.1976.9999]
8. Burešová, O., & Bureš, J. (1982). Radial maze as a tool for assessing the effect of drugs on the working memory of rats. Psychopharmacology, 77(3), 268–71. doi: 10.1007/bf00464578 [DOI:10.1007/BF00464578]
9. Chaudhaery, S. S., Roy, K. K., Shakya, N., Saxena, G., Sammi, S. R., Nazir, A., et al. (2010). Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: Pharmacophore-based virtual screening, synthesis, and pharmacology†. Journal of Medicinal Chemistry, 53(17), 6490–505. doi: 10.1021/jm100573q [DOI:10.1021/jm100573q]
10. Chen, Z., & Kamei, C. (2000). Facilitating effects of histamine on spatial memory deficit induced by scopolamine in rats. Acta pharmacologica Sinica, 21(9), 814-8. PMID: 11501163 [PMID]
11. Cozzolino, R., Guaraldi, D., Giuliani, A., Ghirardi, O., Ramacci, M. T., & Angelucci, L. (1994). Effects of concomitant nicotinic and muscarinic blockade on spatial memory disturbance in rats are purely additive: Evidence from the morris water task. Physiology & Behavior, 56(1), 111–4. doi: 10.1016/0031-9384(94)90267-4 [DOI:10.1016/0031-9384(94)90267-4]
12. Da Silva Costa-Aze, V., Quiedeville, A., Boulouard, M., & Dauphin, F. (2012). 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice. Psychopharmacology, 222(1), 99–115. doi: 10.1007/s00213-011-2627-3 [DOI:10.1007/s00213-011-2627-3]
13. Dash, P. K., Moore, A. N., Kobori, N., & Runyan, J. D. (2007). Molecular activity underlying working memory. Learning & Memory, 14(8), 554–63. doi: 10.1101/lm.558707 [DOI:10.1101/lm.558707]
14. Ebert, & Kirch. (1998). Scopolamine model of dementia: Electroencephalogram findings and cognitive performance. European Journal of Clinical Investigation, 28(11), 944–9. doi: 10.1046/j.1365-2362.1998.00393.x [DOI:10.1046/j.1365-2362.1998.00393.x]
15. Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7(2), 88–95. doi: 10.1016/0006-2952(61)90145-9 [DOI:10.1016/0006-2952(61)90145-9]
16. Falsafi, S. K., Deli, A., Höger, H., Pollak, A., & Lubec, G. (2012). Scopolamine administration modulates muscarinic, nicotinic and NMDA receptor systems. PLoS ONE, 7(2), e32082. doi: 10.1371/journal.pone.0032082 [DOI:10.1371/journal.pone.0032082]
17. Fan, Y., Hu, J., Li, J., Yang, Z., Xin, X., Wang, J., et al. (2005). Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms. Neuroscience Letters, 374(3), 222–6. doi: 10.1016/j.neulet.2004.10.063 [DOI:10.1016/j.neulet.2004.10.063]
18. Fillit, H., Ding, W., Buee, L., Kalman, J., Altstiel, L., Lawlor, B., & Wolf-Klein, G. (1991). Elevated circulating tumor necrosis factor levels in Alzheimer's disease. Neuroscience Letters, 129(2), 318-20. doi: 10.1016/0304-3940(91)90490-k [DOI:10.1016/0304-3940(91)90490-K]
19. Gutierres, J. M., Carvalho, F. B., Schetinger, M. R. C., Agostinho, P., Marisco, P. C., Vieira, J. M., et al. (2014). Neuroprotective effect of anthocyanins on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia in rats. International Journal of Developmental Neuroscience, 33, 88–97. doi: 10.1016/j.ijdevneu.2013.12.006 [DOI:10.1016/j.ijdevneu.2013.12.006]
20. Harrison, F. E., Hosseini, A. H., Dawes, S. M., Weaver, S., & May, J. M. (2009). Ascorbic acid attenuates scopolamine-induced spatial learning deficits in the water maze. Behavioural Brain Research, 205(2), 550–8. doi: 10.1016/j.bbr.2009.08.017 [DOI:10.1016/j.bbr.2009.08.017]
21. Härtl, R., Gleinich, A., & Zimmermann, M. (2011). Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress. Journal of Neurochemistry, 116(6), 1088–96. doi: 10.1111/j.1471-4159.2010.07164.x [DOI:10.1111/j.1471-4159.2010.07164.x]
22. Hauss Wegrzyniak, B., Lynch, M. A., Vraniak, P. D., & Wenk, G. L. (2002). Chronic brain inflammation results in cell lss in the entorhinal cortex and impaired LTP in perforant path-granule cell synapses. Experimental Neurology, 176(2), 336–41. doi: 10.1006/exnr.2002.7966 [DOI:10.1006/exnr.2002.7966]
23. Hritcu, L., Stefan, M., Brandsch, R., & Mihasan, M. (2015). Enhanced behavioral response by decreasing brain oxidative stress to 6-hydroxy-l-nicotine in Alzheimer's disease rat model. Neuroscience Letters, 591, 41–7. doi: 10.1016/j.neulet.2015.02.014 [DOI:10.1016/j.neulet.2015.02.014]
24. Jahanshahi, M., Nickmahzar, E. G., & Babakordi, F. (2013). The effect of Ginkgo biloba extract on scopolamine-induced apoptosis in the hippocampus of rats. Anatomical Science International, 88(4), 217–22. doi: 10.1007/s12565-013-0188-8 [DOI:10.1007/s12565-013-0188-8]
25. Jang, Y. J., Kim, J., Shim, J., Kim, C. Y., Jang, J. H., Lee, K. W., & Lee, H. J. (2013). Decaffeinated coffee prevents scopolamine-induced memory impairment in rats. Behavioural Brain Research, 245, 113–9. doi: 10.1016/j.bbr.2013.02.003 [DOI:10.1016/j.bbr.2013.02.003]
26. Klinkenberg, I., & Blokland, A. (2010). The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neuroscience & Biobehavioral Reviews, 34(8), 1307–50. doi: 10.1016/j.neubiorev.2010.04.001 [DOI:10.1016/j.neubiorev.2010.04.001]
27. Mahmoodi, G., Ahmadi, S., pourmotabbed, A., Oryan, S., & Zarrindast, M. R. (2010). Inhibitory avoidance memory deficit induced by scopolamine: Interaction of cholinergic and glutamatergic systems in the ventral tegmental area. Neurobiology of Learning and Memory, 94(1), 83–90. doi: 10.1016/j.nlm.2010.04.004 [DOI:10.1016/j.nlm.2010.04.004]
28. Marino, M. J., Rouse, S. T., Levey, A. I., Potter, L. T., & Conn, P. J. (1998). Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. Proceedings of the National Academy of Sciences, 95(19), 11465–70. doi: 10.1073/pnas.95.19.11465 [DOI:10.1073/pnas.95.19.11465]
29. Mhatre, M., Floyd, R. A., & Hensley, K. (2004). Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: Common links and potential therapeutic targets. Journal of Alzheimer's Disease, 6(2), 147-57. doi: 10.3233/jad-2004-6206 [DOI:10.3233/JAD-2004-6206]
30. Perry, E. K. (1986). The cholinergic hypothesis—ten years on. British Medical Bulletin, 42(1), 63–9. doi: 10.1093/oxfordjournals.bmb.a072100 [DOI:10.1093/oxfordjournals.bmb.a072100]
31. Sambeth, A., Riedel, W. J., Smits, L. T., & Blokland, A. (2007). Cholinergic drugs affect novel object recognition in rats: Relation with hippocampal EEG. European Journal of Pharmacology, 572(2-3), 151–9. doi: 10.1016/j.ejphar.2007.06.018 [DOI:10.1016/j.ejphar.2007.06.018]
32. Soodi, M., Naghdi, N., Hajimehdipoor, H., Choopani, S., & Sahraei, E. (2014). Memory-improving activity of Melissa officinalis extract in naïve and scopolamine-treated rats. Research in Pharmaceutical Sciences, 9(2), 107-14. PMCID: PMC4311288 [PMID] [PMCID]
33. Soodi, M., Saeidnia, S., Sharifzadeh, M., Hajimehdipoor, H., Dashti, A., Sepand, M. R., & Moradi, S. (2015). Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease. Metabolic Brain Disease, 31(2), 395–404. doi: 10.1007/s11011-015-9773-y [DOI:10.1007/s11011-015-9773-y]
34. Uma, G., & Maheswari, S. U. (2014). Neuroprotective effects of polyherbal formulation (Indian) on noni scopolamineinduced memory impairment in mice. Internation al Journal of Pharmacy and Pharmaceutical Sciences, 6(1), 354-7.