The Role of Medial Prefrontal Cortex and Ventral Tegmental Areas in Withdrawal Syndrome in Morphine Addicted Male Rats

Document Type : Original Article (s)

Authors

1 PhD Student, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

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

3 Professor, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

4 Associate Professor, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: One of the problems of addiction treatment is the relapsing of withdrawal syndrome signs in the addicted person. Rewarding brain regions such as medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) are involved in addiction and onset of withdrawal syndrome. This study was performed to investigate the relationship between these areas in demonstration or relief of withdrawal signs, electrical stimulation and lesion of mPFC, as well as blocking the relative receptors in the VTA.Methods: In an experimental study, 42 male rats weighing 250-300 g were divided in 6 equal groups of control, morphine, and stimulation and lesion electrical receiver groups in mPFC region, and groups receiving the glutamate receptors antagonists by microinjection into the VTA. All of the groups, except the control group, received intraperitoneal morphine during 9 days as the protocol. Finally, on the 10th day, the symptoms of addiction in rats were evaluated.Findings: The electrical stimulation of mPFC significantly increased cycling and scratching (P < 0.01) and bodylifting (P < 0.05) in comparison to the morphine group. Whereas the lesion of this area, and also microinjection of glutamate antagonists into the VTA caused significant decrease of all the withdrawal symptoms in rats.Conclusion: Electrical stimulation of mPFC area increased the withdrawal symptoms in addicted rats, which was most likely due to increase of glutamatergic transmissions into the VTA and reinforcement of reward system; while destruction of this area and blocking of glutamate receptors, probably via decreasing of glutamatergic transmissions, caused decrease of morphine addiction.

Keywords

References

  1. Gholami F, Ebrahim K, Ahmadizad Sj, Dabaq Nikukheslat S, Rahbaran A. The concurrent effect of endurance training and garlic supplementation on body composition and lipid profile in sedentary young males. Med J Tabriz Univ Med Sci 2013; 35(1): 52-9. [In Persian].
  2. Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med 2017; 23(7): 804-14.
  3. Hosseini A, Khoshsovt F, Ahmadi M, Azarbayjani M A, Salehi O, Farkhaie F. Effects of Aloe vera and swimming training on lipid profile of streptozotocin induced diabetic rats. Nutr Food Sci Res 2020; 7(1): 9-16.
  4. Pandey A, Khan HR, Alex NS, Puttaraju M, Chandrasekaran TT, Rudraiah M. Under-carboxylated osteocalcin regulates glucose and lipid metabolism during pregnancy and lactation in rats. J Endocrinol Invest 2020; 43(8): 1081-95.
  5. Mera P, Ferron M, Mosialou I. Regulation of energy metabolism by bone-derived hormones. Cold Spring Harb Perspect Med 2018; 8(6): a031666.
  6. Zoch ML, Clemens TL, Riddle RC. New insights into the biology of osteocalcin. Bone 2016; 82: 42-9.
  7. Liu JJ, Toy WC, Wong MD, Tan CS, Tavintharan S, Wong MS, et al. Elevated undercarboxylated and reduced carboxylated osteocalcin are associated with metabolic syndrome in middle age Asian females. Exp Clin Endocrinol Diabetes 2013; 121(6): 329-33.
  8. Zhou B, Li H, Liu J, Xu L, Guo Q, Zang W, et al. Autophagic dysfunction is improved by intermittent administration of osteocalcin in obese mice. Int J Obes (Lond) 2016; 40(5): 833-43.
  9. Yeap BB, Alfonso H, Chubb SA, Gauci R, Byrnes E, Beilby JP, et al. Higher serum undercarboxylated osteocalcin and other bone turnover markers are associated with reduced diabetes risk and lower estradiol concentrations in older men. J Clin Endocrinol Metab 2015; 100(1): 63-71.
  10. MohammadHossein O, Mohammad F. The role of physical activity and exercise in prevention of non-communicable chronic diseases in Iran. J Isfahan Med Sch 2020; 38(582): 477-88. [In Persian].
  11. Ghorbanian B, Shokrollahi F. The effects of rope training on Paraoxonase-1 enzyme, insulin resistance and lipid profiles in inactive girls. Tehran Univ Med J 2017; 75(4): 307-15. [In Persian].
  12. Davies G, Riemann BL, Manske R. Current concepts of plyometric exercise. Int J Sports Phys Ther 2015; 10(6): 760-86.
  13. Barillas SR, Watkins CM, Wong MA, Dobbs IJ, Archer DC, Munger CN, et al. Repeated plyometric exercise attenuates blood glucose in healthy adults. Int J Exerc Sci 2017; 10(7): 1076-84.
  14. Moreno SD, Brown LE, Coburn JW, Judelson DA. Effect of cluster sets on plyometric jump power. J Strength Cond Res 2014; 28(9): 2424-8.
  15. Rostamizadeh M, Elmieh A, Rahmaninia F. The effect of aerobic and resistance exercises on serum osteocalcin levels, insulin resistance and pancreas beta cell function in overweight men: A clinical trial. J Rafsanjan Univ Med Sci 2019; 18(1): 55-70. [In Persian].
  16. Chahla SE, Frohnert BI, Thomas W, Kelly AS, Nathan BM, Polgreen LE. Higher daily physical activity is associated with higher osteocalcin levels in adolescents. Prev Med Rep 2015; 2: 568-71.
  17. Alipour Y, Abbassi Daloii A, Barari A, Abdi A. Effects of resistance training on serum levels of undercarboxylated osteocalcin, adiponectin and insulin sensitivity in obese women. Tehran Univ Med J 2015; 73(9): 668-73. [In Persian].
  18. Witzke KA, Snow CM. Effects of plyometric jump training on bone mass in adolescent girls. Med Sci Sports Exerc 2000; 32(6): 1051-7.
  19. Singh F, Foster C, Tod D, McGuigan MR. Monitoring different types of resistance training using session rating of perceived exertion. Int J Sports Physiol Perform 2007; 2(1): 34-45.
  20. Birgani GA, Ahangarpour A, Khorsandi L, Moghaddam HF. Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model. Braz J Pharm Sci 2018; 54(2): e17171.
  21. Colleluori G, Napoli N, Phadnis U, Armamento-Villareal R, Villareal DT. Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults. Oxid Med Cell Longev 2017; 2017: 4807046.
  22. Wiklund P, Nordstrom A, Hogstrom M, Alfredson H, Engstrom P, Gustafsson T, et al. High-impact loading on the skeleton is associated with a decrease in glucose levels in young men. Clin Endocrinol (Oxf) 2012; 77(6): 823-7.
  23. Kamali K, Abbassi Daloii A, Abdi A, Ziaolhagh SJ, Barari A. Effect of 8-weeks aerobic training on undercarboxylated osteocalcin, hs-CRP and inisulin resistance in ovreweight women. J Sabzevar Univ Med Sci 2015; 22(5): 823-31. [In Persian].
  24. Franck H, Beuker F, Gurk S. The effect of physical activity on bone turnover in young adults. Exp Clin Endocrinol 1991; 98(1): 42-6.
  25. Mohammad Rahimi GR, Niyazi A, Alaee S. The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int 2020. [Epub ahead of print].
  26. Paschalis V, Nikolaidis MG, Theodorou AA, Panayiotou G, Fatouros IG, Koutedakis Y, et al. A weekly bout of eccentric exercise is sufficient to induce health-promoting effects. Med Sci Sports Exerc 2011; 43(1): 64-73.
  27. Racil G, Zouhal H, Elmontassar W, Ben Abderrahmane A, De Sousa MV, Chamari K, et al. Plyometric exercise combined with high-intensity interval training improves metabolic abnormalities in young obese females more so than interval training alone. Appl Physiol Nutr Metab 2016; 41(1): 103-9.
  28. Sjoberg KA, Frosig C, Kjobsted R, Sylow L, Kleinert M, Betik AC, et al. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling. Diabetes 2017; 66(6): 1501-10.
  29. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130(3): 456-69.
  30. Lin X, Brennan-Speranza TC, Levinger I, Yeap BB. Undercarboxylated osteocalcin: Experimental and human evidence for a role in glucose homeostasis and muscle regulation of insulin sensitivity. Nutrients 2018; 10(7): 847.
  31. Morelli C, Avolio E, Galluccio A, Caparello G, Manes E, Ferraro S, et al. Impact of vigorous-intensity physical activity on body composition parameters, lipid profile markers, and irisin levels in adolescents: A cross-sectional study. Nutrients 2020; 12(3): 742.
  32. Khairandish R, Ranjbar R, Habibi A. Effects of pilates training on body composition, lipid profile and some physical fitness parameters in sedentary obese women. Jundishapur Sci Med J 2018; 17(1): 49-61. [In Persian].
  33. Batacan RB, Duncan MJ, Dalbo VJ, Tucker PS, Fenning AS. Effects of high-intensity interval training on cardiometabolic health: A systematic review and meta-analysis of intervention studies. Br J Sports Med 2017; 51(6): 494-503.
  34. (Vainionpaa A, Korpelainen R, Kaikkonen H, Knip M, Leppaluoto J, Jamsa T. Effect of impact exercise on physical performance and cardiovascular risk factors. Med Sci Sports Exerc 2007; 39(5): 756-63.
  35. Magni P, Macchi C, Sirtori CR, Corsi Romanelli MM. Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases. Clin Chem Lab Med 2016; 54(10): 1579-87.
  36. Bao Y, Zhou M, Lu Z, Li H, Wang Y, Sun L, et al. Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol (Oxf) 2011; 75(2): 196-201.
  37. Chen Y, Zhao Q, Du G, Xu Y. Association between serum osteocalcin and glucose/lipid metabolism in Chinese Han and Uygur populations with type 2 diabetes mellitus in Xinjiang: Two cross-sectional studies. Lipids Health Dis 2017; 16(1): 139.
Journal of Isfahan Medical School
Volume 38, Issue 594 - Serial Number 594
September and October 2020
Pages 736-744

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History

  • Receive Date: 09 July 2020
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

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