Effect of Physical Activity on Symptoms of Morphine Addiction in Rats, after and before of Lesion of the mPFC Area

Document Type: Original Article


1 Department of Basic Sciences, Isfahan Payam -e -Noor University, Isfahan, Iran

2 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Basic Sciences, Islamic Azad University, Khorasgan Branch, Isfahan, Iran

4 Department of Basic Sciences, Isfahan Payam-e- Noor University, Isfahan, Iran



Drug addiction is one of the fastest growing social problems that researchers, for many years, have been trying to find proper strategies for its prevention and treatment. Short-term physical activity is considered as acceptable for the treatment and prevention of addiction. On the other hand, prefrontal cortex is known to be responsible for many of the complex behavioral responses, especially those relevant to addiction and drug abuse. In this study, the effects of short-term physical activity (treadmill running) on withdrawal symptoms in rats, with or without medial Prefrontal Cortex (mPFC) area was evaluated.
Materials and Methods:
In this experimental study, male Wistar rats, weighing 250-300 g. Were selected and divided into four groups: control, sham, test1 and test 2 groups, with one group having a surgery (test 2). In order to study the effects of short-term physical activity, we employed a treadmill with the adjustable speed of 17 m/min, and a 15% incline. Following the injection of three different doses of morphine (10, 20 and 40 mg/Kg) for 9 days, treadmill running was completed on the tenth day and then the symptoms of addiction were evaluated.
Administration of morphine as aforementioned, and treadmill running on rats with mPFC area, significantly alleviated some of the symptoms and signs, such as, bruxism, cycling, body lift, licking, standing and scratching (P<0.05). Therefore, there are noticeable differences in these symptoms between the exercise and morphine groups (P<0.05).
: We propose that when using morphine mPFC plays an important role in the reduction of reward symptoms. Running lessens the effects of morphine. Moreover, short-term physical activity might decrease the tendency to use morphine in those with mPFC area, compared to other groups, especially with the one undergoing an mPFC operation.


1. Nestle EJ. Neurobiology Learn. Common molecular and cellular substrates of addiction and memory. Neurobiol Learn Mem 2002; 78:637-647.

2. Kimmie Mc, Marnie Walk away from depression. 2005. The West Australian (perth), online.

3. Meeusen R,Piacentini De Meirleir K. Brain microdialysis in exercise research. Sports Med 2001; 31:965-983

4. Azizi Malekabadi H, Alaei H, Oryan S.The effect of exercise (treadmill running) on glutamate concentration variation of hippocampal dentate gyrus in the intact and morphine dependent male rats. Iran J Basic Med Sci 2007; 32:250-259.

5. Bequet F, Gomez- Merino D, Bertheiot M, Guezennec CY. Exercise-induced changes in brain glucose supplementation and serotonin revealed by microdialysis in rat hippocampus. Acta Physiol Scand 2001; 173:223-230.

6. Meeusen R, Piacentini MF, Van Den ES, Magnus L, De MK. Exercise performance is not influenced by a 5-HT reuptake inhibitor. Int J Sports Med 2001; 22:329-336.

7. Azizi Malekabadi H, Alaei H,Hsseini M.The effect of short-term physical activity(treadmill running) on spatial learning and memory in the intact and

Physical Activity and Morphine Addiction Saedi-Marghmaleki et al

Iran J Basic Med Sci, Vol. 16, No. 10, Oct 2013



morphine dependent male rats. J Isfahan Med School 2008; 26:89.

8. Kavoosi Z, Fereidoni M , Moghimi A, SadeghA. 2009. Effect of administration of ultra low doses of morphine on learning processes and spatial memory retention in morris water maze in rat. 19th Iranian congress of Physiology and Pharmacology; Tehran: 3-6 November 2009.

9. Poulsen FR, Meyar M, Rasmussen JZ. Generation of new nerve cells in the adult human brain. Ugeskr Laeger 2003; 165:1443-1447.

10. Berke JD, Hyman SE. Addiction, dopamine, and the molecular mechanisms of memory. Neuron 2000; 25:515–532


11. Fuentealba JA, Forray MI, Gysling K. Chronic morphine treatment and withdrawal increase extracellular levels of norepinephrine in the rat bed nucleus of the stria terminalis. J Neurochem 2000; 75:741–748 (Aug.)

12. Berke JD, Hyman SE. Addiction, dopamine, and the molecular mechanisms of memory. Neuron 2000; 25:515–532.

13. Alaei H, Borjeian L, Azizi M, Orian S, Pourshanazari A, Hanninen O. Treadmill running reverses retention deficit induced by morphine. Eur J Pharmacol 2006; 536:138–141.

14. Paxinos G, Watson C. The rat brain in streotaxic coordinates. 5 th ed. SanDiego: Academic Press; 2006.p.40-144.

15. Koyuncuoglu H, Nurten A, Enginar N, Ozerman B, Kara I. The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence. Pharmacol Res 2001; 43:245–250.

16. Alaei H, Moloudi R, Sarkaki A, Azizi-Malekabadi H, Hanninen O. Daily running promotes spatial learning and memory in rats. J Sports Sci Med 2007; 6:429-433.

17. Mathes WF, Kanarek RB.Chronic running wheel activity attenuates the antinociceptive actions of morphine and morphine-6-glucoronide administration into the periaqueductal gray in rats. Pharmacol Biochem Behav 2006; 78:584.

18. Haghparast A, Esmaeili A. Effects of morphine and lidocaine administration into the cuneiformis nucleus of rats on acute and chronic pain modulation by formalin test. J Birjand Univ Med Sci 2007; 14:5-12.

19. Haghparast A, Alizadeh A, Motamedi F. Effect of subcutaneous morphine injection on neuronal activity in the nucleus cuneiformis of rat. Neuroscience Research, Center, Shahid Beheshti University of Medical Sciences and Services Tehran, Iran.Accepted:22, November, 2008; 34-39

20. Hoveida R, Alaei H, Oryana S, Parivara K, Reisi P. Treadmill running improves spatial memory in an animal model of Alzheimer’s disease.

2011; 216: 270–274.

21. Lett BT, Grant VL, Koh MT, Flynn G.Prior experience with wheel running produces cross-tolerance to the rewarding effect of morphine. Pharmacol. Biochem Behav 2001; 101-105.

22. Govern Mc MK

. The effect of exercise on the brain. Biology 5002; 202.

23. Aiaei H, Esmaeili M, Nasimi A. Pourshanazari A. Ascorbic acid decreases morphine self-administration and withdrawal symptom in rats. Pathophysiology 2005; 12:103-107.

24. Pourshanazari AA, Alaei H, Rafati A. Effect of electrical stimulation of nucleus raphe dorsalis on initiation of morphine self-administration in rats. Med J Islamic Acad Sci 2000; 13:63-67.

25. Esch T, Stefano GB. The neurobiology of pleasure,rewaed processes, addiction and their health implication . Neuro Endocrinol Lett 25:235-51.

26. Cereb J, Ouchi Y, Yoshikawa E, Futatsubashi M, Okada H, Torizuka T, et al. Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects:a positron emission tomography study. Blood Flow Metab 2002; 22:746-752.

27. Fisher BE, Petzinger GM, Nixon K, Hogg E, Bremmer S, Meshul CK, et al. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned mouse basal ganglia;. J Neurosci Res 2004; 77:378-390.

28. Tzchentke TM, Department of pharmacology Research and Development, Grünenthal Gmbh, Aachen, Federal Republic of Germany. The medial prefrontal cortex as a part of the brain reward system. Review Article Amine Acids 5000; 19:211-219.

29. Alaeia H, Moloudia R, Sarkaki A. Effects of treadmill running on mid-term memory and swim speed in the rat with Morris water maze test.

2008; 12, 72–75.

30. Ahmadiasl N, Alaei H, Hänninen O. Effect of exercise on learning, memory and levels of 2.epinephrine in rats’ hippocampus. J Sports Sci Med 5003; 5:106-109.

31. Uysal N, Tugyan K, Kayatekin BM, Acikgoz O, Bagriyanik HA, Gonenc S, et al. The effects of regular aerobic exersice in adolescent period on hippocampal neuron density-apoptosis and spatial memory. Neurosci lett 2005; 383:241-245.