Increased relative gene expression of Proopiomelanocortin (POMC) and Melanocortin 4 Receptor (MC4R) following aerobic exercise and psilocybin in female Wistar rats poisoned with Crystal (Methamphetamine)

Subject Areas : Plasma biomarkers

Daniel Hakkak ¹ , رامبد خواجه ای ² , Sayyed-Javad Ziaolhagh ³ , اکبر صقی پور افشار ⁴

1 - Ph.D. student, Department of Sports Sciences, Islamic Azad University, Neyshabur branch, Iran
2 - دانشگاه ازاد اسلامی واحد نیشابور. خراسان رضوی
3 - Assistant Professor, Sports Science Department, Islamic Azad University, Shahroud Branch, Iran
4 - دانشگاه ازاد اسلامی واحد نیشابور

Received: 2024-07-05 Accepted : 2024-08-30 Published : 2024-11-14

Keywords: Crystal, methamphetamine, psilocybin, aerobic physical activity, proopiomelanocortin, melanocortin 4 receptor,

Abstract :

Crystal (Methamphetamine) is a drug and stimulant of the central nervous system that directly affects the brain and has significant effects on a person's eating behavior. 30 female Wistar rats were selected according to weight and age conditions and divided into 5 groups (n=6) 1- healthy control 2- received methamphetamine 3- methamphetamine + aerobic activity 4- methamphetamine + psilocybin 5- methamphetamine + aerobic activity + psilocybin were divided. Intraperitoneal induction of methamphetamine with a dose of 10 mg and induction of psilocybin with a dose of 0.025 mg/kg was considered intraperitoneally. The aerobic exercise program included 4 weeks of running on a treadmill at a speed of 25 meters per minute for 30 minutes and 6 days a week in methamphetamine addicted groups. The brain tissue was sent to the relevant laboratory to investigate the expression of proopiomelanocortin (POMC) and melanocortin 4 receptor (MC4R) genes. Relative fold change calculation method was used for gene expression analysis. The results showed that induction of methamphetamine increases the expression of POMC gene by 166% and MC4R by 44%. In addition, both interventions decreased the expression of both genes, and of course, the combination of both interventions resulted in synergy and improvement of these genes. On the other hand, comparing two interventions, it seems that aerobic physical activity is more effective than psilocybin mushroom in reducing the expression of both genes. It seems that the induction of methamphetamine reduces the genes involved in increasing appetite and falsely stimulates satiety. On the other hand, the present study showed that the combination of aerobic activity and psilocybin increases appetite and suppresses the progressive increase of satiety genes in the hypothalamus. Comparing each, physical activity seems to be more effective than psilocybin.

References:

1. Hersi M, Corace K, Hamel C, Esmaeilisaraji L, Rice D, Dryburgh N, et al. Psychosocial and pharmacologic interventions for problematic methamphetamine use: Findings from a scoping review of the literature. Plos one. 2023;18(10):e0292745.
2. Edinoff AN, Kaufman SE, Green KM, Provenzano DA, Lawson J, Cornett EM, et al. Methamphetamine use: a narrative review of adverse effects and related toxicities. Health Psychology Research. 2022;10(3).
3. İvecen B, Gokdemır O. Methamphetamine addiction. DAHUDER Medical Journal. 2022;2(4):98-101.
4. Zuloaga DG, Jacobskind JS, Raber J. Methamphetamine and the hypothalamic-pituitary-adrenal axis. Frontiers in neuroscience. 2015;9:178.
5. Dunigan AI, Roseberry AG. Actions of feeding-related peptides on the mesolimbic dopamine system in regulation of natural and drug rewards. Addiction neuroscience. 2022;2:100011.
6. Chen Y. Regulation of food intake and the development of anti-obesity drugs. Drug discoveries & therapeutics. 2016;10(2):62-73.
7. Landry T, Shookster D, Chaves A, Free K, Nguyen T. Energy Feeding Status Behavior Differentially and POMCARC Modifies Neuron Activity After Acute Treadmill Exercise in Untrained Mice. Central Regulation of Metabolism. 2022.
8. Ribeiro FM, Silva MA, Lyssa V, Marques G, Lima HK, Franco OL, Petriz B. The molecular signaling of exercise and obesity in the microbiota-gut-brain axis. Frontiers in Endocrinology. 2022;13:927170.
9. Concepción-Zavaleta MJ, Quiroz-Aldave JE, Durand-Vásquez MdC, Gamarra-Osorio ER, Valencia de la Cruz JdC, Barrueto-Callirgos CM, et al. A comprehensive review of genetic causes of obesity. World Journal of Pediatrics. 2024;20(1):26-39.
10. Fadahunsi N, Lund J, Breum AW, Mathiesen CV, Larsen IB, Knudsen GM, et al. Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice. Translational psychiatry. 2022;12(1):330.
11. Downey AE, Chaphekar AV, Woolley J, Raymond-Flesch M. Psilocybin therapy and anorexia nervosa: a narrative review of safety considerations for researchers and clinicians. Journal of Eating Disorders. 2024;12(1):49.
12. Borgland SL, Neyens DM. Serotonergic psychedelic treatment for obesity and eating disorders: potential expectations and caveats for emerging studies. Journal of Psychiatry and Neuroscience; 2022. p. E218-E21.
13. Tokunaga I, Kubo S-i, Ishigami A, Gotohda T, Kitamura O. Changes in renal function and oxidative damage in methamphetamine-treated rat. Legal medicine. 2006;8(1):16-21.
14. Risca HI. Preclinical behavioral assessment of chronic, intermittent low-dose psilocybin in rodent models of depression and anxiety: Western Michigan University; 2021.
15. Sajadi A, Amiri I, Gharebaghi A, Komaki A, Asadbeigi M, Shahidi S, et al. Treadmill exercise alters ecstasy-induced long-term potentiation disruption in the hippocampus of male rats. Metabolic Brain Disease. 2017;32:1603-7.
16. Adler M, Alon U. Fold-change detection in biological systems. Current Opinion in Systems Biology. 2018;8:81-9.
17. Harricharan R, Abboussi O, Daniels WM. Addiction: A dysregulation of satiety and inflammatory processes. Progress in brain research. 2017;235:65-91.
18. Zhou Y, Lu Y, Jin X, Liu J, Finlayson G, Zhou C. Effects of moderate-and high-intensity acute aerobic exercise on food reward and appetite in individuals with methamphetamine dependence. Physiology & behavior. 2019;211:112649.
19. Bello NT, Kshatriya D. Central nervous system stimulants and drugs that suppress appetite. Side Effects of Drugs Annual. 41: Elsevier; 2019. p. 1-11.
20. Xu C, Zhang Z, Hou D, Wang G, Li C, Ma X, et al. Effects of exercise interventions on negative emotions, cognitive performance and drug craving in methamphetamine addiction. Frontiers in Psychiatry. 2024;15:1402533.
21. Fatima MT, Ahmed I, Fakhro KA, Akil ASAS. Melanocortin‐4 receptor complexity in energy homeostasis, obesity and drug development strategies. Diabetes, Obesity and Metabolism. 2022;24(4):583-98.
22. Love S, Nicolls M, Rowland B, Davey J. The impact of methamphetamine use and dependence: A systematic review on the cognitive-behavioural implications for road safety. Transportation Research Part F: Traffic Psychology and Behaviour. 2024;103:480-99.
23. Shevchouk OT, Tufvesson-Alm M, Jerlhag E. An overview of appetite-regulatory peptides in addiction processes; from bench to bed side. Frontiers in Neuroscience. 2021;15:774050.
24. Hsieh YS, Chen PN, Yu CH, Kuo DY. Central dopamine action modulates neuropeptide‐controlled appetite via the hypothalamic PI3K/NF‐κB‐dependent mechanism. Genes, Brain and Behavior. 2014;13(8):784-93.
25. Sustkova-Fiserova M, Charalambous C, Khryakova A, Certilina A, Lapka M, Šlamberová R. The role of ghrelin/GHS-R1A signaling in nonalcohol drug addictions. International Journal of Molecular Sciences. 2022;23(2):761.
26. Zhang X, Gao Y, Tang N, Qi J, Wu Y, Hao J, et al. One evidence of cocaine-and amphetamine-regulated transcript (CART) has the bidirectional effects on appetite in Siberian sturgeon (Acipenser baerii). Fish physiology and biochemistry. 2018;44:411-22.
27. Kobeissy FH, Jeung JA, Warren MW, Geier JE, Gold MS. Preclinical Study: Changes in leptin, ghrelin, growth hormone and Neuropeptide‐Y after an acute model of MDMA and methamphetamine exposure in rats. Addiction biology. 2008;13(1):15-25.
28. Rodrigues KCDC, Pereira RM, Campos TDd, Moura RFd, Silva ASd, Cintra DE, et al. The role of physical exercise to improve the browning of white adipose tissue via POMC neurons. Frontiers in Cellular Neuroscience. 2018;12:88.
29. Benite-Ribeiro SA, Putt DA, Santos JM. The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control. Medical Hypotheses. 2016;93:30-3.
30. Smith JK. Exercise, obesity and CNS control of metabolic homeostasis: a review. Frontiers in physiology. 2018;9:339961.
31. Shojaei M. Systematic Revier Article: A Systematic Review of the Relationship Between Sex Hormones and Leptin and Insulin Resistance in Men. artery. 2024;3(2).
32. Beaulieu K, Blundell JE, van Baak MA, Battista F, Busetto L, Carraça EV, et al. Effect of exercise training interventions on energy intake and appetite control in adults with overweight or obesity: A systematic review and meta‐analysis. Obesity reviews. 2021;22:e13251.
33. Halliday TM, White MH, Hild AK, Conroy MB, Melanson EL, Cornier M-A. Appetite and energy intake regulation in response to acute exercise. Medicine and science in sports and exercise. 2021;53(10):2173.
34. Yavarpanah F, Rajabi S, Ziaolhagh SJ. The Effect of Psilocybin and Aerobic Exercise on the Gene Expression of PARP and Dopamine 5 Receptor in Heart Tissue of Female Rats Addicted to Methamphetamine. Journal of Isfahan Medical School. 2023;41(741):946-52.
35. Reichelt A. Complexities of psychedelics for therapeutic use in obesity and eating disorders. Journal of Psychiatry and Neuroscience. 2022;47(5):E366-E.