Document Type : Research Paper



The aim of this study was to investigate the effect of forced physical exercise with moderate intensity on Alzheimer-induced amnesia in adult male rats. 48 male Wistar- Albino rats were randomly selected and assigned to 6 groups (n=8 per group): control, placebo (saline), drug-exercise, saline-exercise, exercise and exercise-drug. In this study, Dicyclomine (16 mg/kg) was used to induce Alzheimer-like amnesia and moderate exercise (60 minutes per day × 30 days). The rats were trained and tested using Morris water maze­. The findings showed that the group receiving Dicyclomine increased­ delay in reaching the platform­ in acquisition (P=0.044) and recall (P=0.031) compared with exercise, control and saline groups. But there were no significant differences between exercise and exercise-saline groups compared with exercise-Dicyclomine group. Also, a significant difference (delay in reaching the platform) was observed between Dicyclomine-exercise, saline-exercise compared with Dicyclomine in acquisition (P=0.005) and recall (P=0.002). In conclusion, this study showed that memory and learning in the acquisition and recall phases were destroyed by Dicyclomine and 30 sessions of moderate-intensity running (forced) could prevent memory corruption.


1. رحمانی، احمد؛ شیخ، محمود؛ حمایت‌طلب، رسول و نقدی، ناصر (1392)." تأثیر ورزش بر تغییرات یادگیری متعاقب استرس". مجلۀ علمی پژوهشی دانشگاه علوم پزشکی اراک،­ سال ­16،­ ش1 ­( شمارۀ پیاپی70)، ص 64-52.
2. Adlard, P.A., Perreau,­V.M., Pop V., Cotman, C.W. (2005). "Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease". J Neurosci.,25:4217–4221.
3. Anderson, B.J., Rapp, D.N., Baek, D.H., McCloskey, D.P., Coburn-Litvak, P.S., Robinson, J.K.­)2000(. "Exercise influences spatial learning in the radial arm maze". Physiology and Behavior., 70, 425–429.
4­. Ang, E.T., Dawe­, S.D., Wong, T.H., Moochhala, S., Ng, Y.K. (2006).­"Alterations in spatial learning and memory after forced exercise". B­r­a­­in R­esearch., 1­1­1­3 , 1­8­6 – 1­93.
5. Babri­, S., Reisi, P., Alaei­, H., Sharifi, M., Mohades, ­G.(­2008). "Effect of forced treadmill exercise on long-term potentiation (LTP) in the dentate gyrus of hippocampus in male rats". Physiology and Pharmacology.,­12(1),­39­–­45.
6. Barnes, C.A., Forster, M.J., Fleshner, M.­, Ahanotu, E.N.,­ Laudenslager, M.L., Mazzeo, ­R.S.(1991)."Exercise does not modify spatial memory, brain autoimmunity, or antibody response in aged F-344 rats". Neurobiol Aging,12(1):47-53.
7. Blustein, ­J.F., ­Mclaughlin, M. and Holfman, J.R.(2006)."Exercise effects stress-induced analgesia and spatial learning in rats". Physiol Behav.­,89: 582–586.
8. Cotman, C.­W., & Berchtold, N.­C. (2002). "Exercise: A behavioral intervention to enhance brain health and plasticity".Trends in Neurosciences.,­25(6),­130-125.
9. Cotman, C.W., Berchtold, N.C., Christie, L.A, (2007)."­Exercise builds brain health: key roles of growth factor cascades and inflammation". Trends Neurosci., 30­(9) 464-72.
10. Cotman, C.­W., Nicole, C., Berchtold, N.C.­(2007)."Physical activity and the maintenance of cognition: Learning fromanimal models". Alzheimer’s & Dementia., 3, 30–37.
11. Erickson, K.I., Voss, M.W., Prakash, R.S., Basak, C., Szabo, A., Chaddock, L., Kim, J.S., Heo, S., Alves, H., White. S.M., Wojcicki,­T.R., Mailey, E., Vieira, V.J., Martin, S.A., Pence, B.D., Woods, J.A., McAuley, E., Kramer, A.F.(2011)."Exercise training increases size of hippocampus and improves memory". Neuroscience, Proc Natl Acad Sci U S A., 108(7): 3017–3022.
12.Fordyce, D.E., Farrar, R.P.(1991)."Physical activity effects on hippocampal and parietal cortical cholinergic function and spatial learning in F344 rats". Behav Brain Res,.43(2):115–23.
13. Fornari,R.V., Moreira, K.M., Oliveira,­M.G.M.­(2000),"Effects of the selective M1 muscarinic receptor antagonist dicyclomine on emotional memory". Learn. Mem., 7,­287–292.
14. Gage, F.H., Kelly, P.A., Bjorklund, A. (1984)." Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats". J Neurosci. , 4:2856 –2866.
15. García-­capdevila, S., Portell-Cortés, I., Torras-Garcia, M., Coll-Andreu.M., Costa, Miserachs, D.­(2009). "Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise". Behavioural Brain Research., 202­,(2) 162–170.
16. Geinisman, Y., de Toledo-Morrell, L., Morrell, F., Persina, I.S., Rossi, M. (1992)." Age-related loss of axospinous synapses formed by two afferent systems inthe rat dentate gyrus as revealed by the unbiased stereological dissector technique". Hippocampus., 2 (4),437– 444.
17. Ghelardini, C., Galeotti, N., Matucci, R., Bellucci, C., Gualtieri, F., Capaccioli, S., Quattrone, A., and Bartolini, A. (1999)." Antisense knockdowns of M1 receptors induces transient anterograde amnesia in mice". Neuropharmacology., 38: 339–348.
18. Giachetti, A., Giraldo, E., Ladinsky, H., and Montagna, E. (1986). "Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine". Brit. J. Pharmac., 89: 83–90
19. Gold, P.E.­(2003)"Acetylcholine modulation of neural systems involved in learning and memory". Neurobiology of Learning and Memory., 80, 194- 210.
20. Hasselmo, M.E. (2006).­ "The role of acetylcholine in learning and memory". Curr Opin Neurobiol.,16, 710- 705.
21. Hill, R.D., Storandt, M., Malley, M.­(1993)."The impact of­ long-term exercise training on psychological function in older adults". J­ Gerontol., 48 (1) 12–17.
22. Jafari-Sabet, M. (2006)." 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". Behavioural Brain Research .,169 , 120- 127.
23. Kannangara, T.­S.­, Lucero, M.J., Gil-Mohapel, J., Drapala, R.J., Simpson, J.M.,­ Christie , B.R., van Praag,H. (2011­(.­" Running reduces stress and enhances cell genesis in aged mice". Neurobiology of Aging., 32(12),2279-86.
24. Kim, Y. P., Kim­, ­­­H.­B., Jang­, ­M. H., Lim, ­B.V., Kim, Y. J.­, Kim­, H., Kim ,­ S.­S., Kim­,­E. H., Kim, C. J.­(2003). "Magnitude- and Time-Dependence of the Effect of Treadmill Exercise on Cell Proliferation in the Dentate Gyrus of Rats". International Journal of Sports Medicine., 24(02):114-7.
25. Kim,­Y.P.­,­Shin, M.S.,­ ­Chang,­­HK.­, Jang, M.H., Lee, S.J.­, Lee, H.H.­, Yoon J.H., Jeong,I.G., Kim,C.J.( 2004)." Age-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats". Neuroscience Letters.,Volume 355., 1–2. Pages 152–154.
26. Leasure, J.L., Jones.(2008). "Forced and voluntary exercise differentially affect brain and behavior". Neuroscience.,Volume 156, Issue 3, 15, Pages 456–465.
27. Mayeux, R. ( 2003). "Epidemiology of neurodegeneration". Annu Rev Neurosci., 26: 81-104.
28. Mello, P.B., Benetti, F., Cammarota, M., Izquierdo, I. (2008). "Effects of acute and chronic physical exercise and stress on different types of memory in rats". Anais da Academia Brasileira de Ciências., 80(2): 301-309.
29. Mitchell, A.S., Dalrymple-Alford, J.C., Christie, M.A. (­2002). "Spatial working memory and the brainstem cholinergic innervation to the anterior thalamus". J Neurosci., 22:1922–8.
30. Molteni, R., Ying, Z., Gomez-Pinilla, ­F. (2002). "Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray". Eur J Neurosci., 16 1107–1116.
.31 Monteiro Moreira K1, Lima Ferreira T, Vecchio Fornari R, Perez Figueredo LZ, Menezes Oliveira MG. Monteiro,­ M­.­K.,­ Lima, F.T., Vecchio F.R., Perez Figueredo, L.Z., Oliveira, M.G.(2005)."Interaction between M1- muscarinic and glutamatergic NMDA receptors on an inhibitory avoidance task". Brain Research Bulletin., 67 (2005) 504–50.
32.Morris, J.C. (1996)."Classification of dementia and Alzheimer ­disease". Acta Neurol Scand Suppl., 16541-50
33. Parsa­,N. (2011)."Alzheimer ’s disease: A medical challenge of 21st century". National Institutes of Health, Ministry of Health., USA., 14(55):100-108 Arak Medical University Journal AMUJ.
34. Pereira, A. C., Huddleston, D. E., Brickman, A. M., Sosunov, A. A., Hen, R., McKhann, G. M., et al. (2007). "An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus". Proceedings of the National Academy of Sciences of the United States of America., 104(13), 5638-5643.
35. Pietropaolo, S., Sun,Y., Li, R., Brana, C., ­Feldon, J.,­Yee, B.K.(2008). "The impact of voluntary exercise on mental health in rodents: A neuroplasticity perspective". Behavioural Brain Research 192 , 42–60
36. Quaney, B.M., Boyd, L.A., ­McDowd, J.M., Zahner,­L.H., He,­ J.,­ Mayo, M.S and Macko, RF.(2009). "Aerobic Exercise Improves Cognition and Motor Function Poststroke". Neurorehabil Neural­., 23(9): 879–885.
37. Radak, Z., Kaneko, T., Tahara, S., Nakamoto, H., Pucsok, J.,Sasvari, M., et al. (2001). "Regular exercise improves cognitive function and decrease oxidative damage in rat brain".Neurochemistry International., 338(1), 17-23..
38. Radak. Z., Told, A., Szabo, Z., Siamilis, S., Nyakas, C., Silye, G., Jakus, J. and Goto, S. (2006). "The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain". Neurochem Internat., 49: 387–392.
39. Rovio, S., Kareholt, I., Helkala, E.L., Viitanen, M., Winblad, B., Tuomilehto, J., Soininen, H., Nissinen, A., Kivipelto, M. (2005)." Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease". Lancet Neurol., 4:705–711.
40.­Salim, S., Sarraj, ­N.,­Taneja, M., Saha, K., Tejada-Simon, M.V., Chugh, G. (2010)."Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats", Behavioural Brain Research., 208 545–552.
41. Scarpini, E­., Scheltens, P., Feldman, H.(2003)." Treatment of Alzheimer’s disease: current status and new perspective." THE LANCET Neurology., Vol 2­, 539-47.
42. Sitaram,­ N., Weingartner, H., Gillin, J.C. ­(1978)." Human serial learning: enhancement with arecholine and choline impairment with scopolamine". Science .,201:274–6.
43.­Snigdha, S., Rivera­, C., Milgram, N.W and Cotman, C.­W. (2014)." Exercise enhances memory consolidation in the aging brain". Frontiers in Aging Neuroscience., Volume6 , Article 3.
44.­Studenski, S., Carlson, M.C., Fillit, H. (2006). "From Bedside to Bench: Does mental and Physical activity promote cognitive vitality in late life?" Sci.Aginy Knoul., Enuiron. (10), pe21.
45.Um, H.S.­, Kang, E.B., Leem, Y.H., Cho, I.H., Yang, C.H., Chae, K.R., Hwang, D.Y, Cho, J.Y. (2008)." Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model". International Journal of Molecular Medicine.,­ Volume: 22, Issue: 4, Pages: 529-539.
46. Uysal, N., Tugyan, K., Kayatekin, B.M., Acikgoz, O., Bagriyanik, H.A., Gonenc, S., et al.(2005)."­The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory". Neurosci Lett.,383(3):241–5.
47. Van Praag, H., Christie, B.R.,­ Sejnowski, T.J. ­and Gage, F.H. (1999)." Running enhances neurogenesis, learning, and long-term potentiation in mice". Proc Natl Acad Sci U S A., vol. 96 , no. 23 ,­13427–13431
48. Winter, B.,­ Breitenstein, C., Mooren, F.C.,­ Voelker, K., Fobker, M.,­ Lechtermann, A.,­­ ­Krueger, K., Fromme, A.,­ Korsukewitz, C.,­ Floel, Agnes.,­ Knecht, S.(2007)." High impact running improves learning". Neurobiol Learn Mem., Volume 87, Pages 597–609.
49. Wong-Goodrich, S.J., Pfau, M.L., Flores, C.T., Fraser, J.A., Williams, C.L., Jones, L.W.­ (2010)." Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation". US National Library of Medicine National Institutes of Health., (22):9329-38.
50. WorldAlzheimerReport. (2013).­ "Alzheimer's DiseaseInternational".The Global Economic Impact of Dementia The regional distribution of global costs 39., In last year's World Alzheimer Report, Alzheimer's Disease International estimated that there are,.
51. Wyss, J.M., Chambless, B.D., Kadish, I., van Groen, T.­(2000). "Age related decline in water maze learning and memory in rats:strain differences". Neurobiol Aging.,Vol.­21­,671–681.
52. Young, R.J.(1979). "The effect of regular exercise on cognitive functioning and personality". British Journal of Sports Medicine13,(3)­110–117.
53. Yuede, C.M.­, Zimmerman, S.D., Dong,­H., Kling, M.J., Bero, A.W., Holtzman, D.M., Timson,­ B.F., Csernansky, J.G.­(2009)."­Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease". Neurobiology of Disease.,35 (3): 426–432.