Ascorbic acid effect on morphine withdrawal symptoms in rats
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Abstract
Introduction: Today, drug addiction is an important healthcare issue. Any helps to drug withdrawal may decrease its prevalence in the society. Ascorbic acid is a component, which can affect neurotransmitter systems as a regulator along with its cofactor role. Noradrenergic and dopaminergic systems are two important neurotransmitter systems in the opiate withdrawal syndrome. It seems that ascorbic acid can decrease the symptoms of opiate withdrawal through regulating the related systems. In this regard, the current study aimed to evaluate the effect of ascorbic acid on the symptoms of morphine withdrawal in Syrian mice. Materials and Methods: Male Syrian mice in eight experimental groups received incremental doses of morphine as 10, 20, 30 and 40mg/kg within the first, second, third, and fourth days of the experiment, respectively, through intraperitoneal injection, twice a day, and the control group received and equal amount of saline. On the fifth day, six groups of morphine addicts received ascorbic acid with six doses of 10, 50, 100, 200, 400 and 800mg/kg through intraperitoneal injection. Then, naloxone 2mg/kg was injected to all groups including morphine alone and morphine with acute does of ascorbic acid. Then, withdrawal symptoms were evaluated for 30 minutes. Results: Administration of an acute dose of ascorbic acid reduced dose dependent withdrawal symptoms in such a way that 10, 50, and 100mg/kg doses of ascorbic acid reduced “writhing” symptom, 200mg/kg reduced “jumping” symptom, and 400 and 800mg/kg reduced “climbing, jumping, and standing” symptoms. Conclusion: It seems that ascorbic acid administration can improve the symptoms of opiate withdrawal syndrome. More studies on human population can also indicate the therapeutic effect of ascorbic acid on drug withdrawal. Keywords: Addiction; Morphine; Withdrawal syndrome; Ascorbic acid.
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16. Kosten, T.R. and T.P. George, The neurobiology of opioid dependence: implications for treatment. Science & practice perspectives, 2002. 1(1): p. 13.
17. Zeraati, F., M. Araghchian, and M.H. Farjoo, Ascorbic Acid interaction with analgesic effect of morphine and tramadol in mice. Anesthesiology and pain medicine, 2014. 4(3).
18. Sepulveda, M.J., et al., Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: an in vivo microdialysis study. Pharmacology Biochemistry and Behavior, 1998. 60(1): p. 255-262.
19. Langerman, L., et al., A method of reducing the opioid withdrawal intensity using progressively increasing doses of naloxone. Journal of pharmacological and toxicological methods, 1999. 42(3): p. 115-119.
20. Fritz, H., et al., Intravenous vitamin C and cancer: a systematic review. Integrative cancer therapies, 2014. 13(4): p. 280-300.
2. Iovcheva, M., S. Zlateva, and M. Asparuhova, Precipitated withdrawal reaction to opiates in cases of improper use of naltrexone. Addict Biol, 2007. 1: p. 75-77.
3. Radke, A.K., P.E. Rothwell, and J.C. Gewirtz, An anatomical basis for opponent process mechanisms of opiate withdrawal. Journal of Neuroscience, 2011. 31(20): p. 7533-7539.
4. Richardson, K.A., et al., Neonatal animal models of opiate withdrawal. ILAR journal, 2006. 47(1): p. 39-48.
5. Narita, M., M. Funada, and T. Suzuki, Regulations of opioid dependence by opioid receptor types. Pharmacology & therapeutics, 2001. 89(1): p. 1-15.
6. Rebec, G.V. and R.C. Pierce, A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission. Progress in neurobiology, 1994. 43(6): p. 537-565.
7. Alaei, H., et al., Ascorbic acid decreases morphine self-administration and withdrawal symptoms in rats. Pathophysiology, 2005. 12(2): p. 103-107.
8. Gu, P.F., et al., Frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not the nucleus accumbens of freely moving rats. Brain research, 2005. 1033(2): p. 194-201.
9. Schauss, A.G., Attenuation of heroin withdrawal syndrome by the administration of high-dose vitamin C. JOM, 2012. 27(4): p. 189.
10. Kulkarni, S., C. Deshpande, and A. Dhir, Ascorbic acid inhibits development of tolerance and dependence to opiates in mice: Possible glutamatergic or dopaminergic modulation. Indian journal of pharmaceutical sciences, 2008. 70(1): p. 56.
11. Bélanger, M., I. Allaman, and P.J. Magistretti, Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell metabolism, 2011. 14(6): p. 724-738.
12. Nakai, T., et al., Noradrenaline release in rat locus coeruleus is regulated by both opioid andα2-adrenoceptors. Pharmacological research, 2002. 45(5): p. 407-412.
13. Rafati, A., M. Dashti, and A. Morshedi, The role of vitamin C on prevention of morphine addiction in rats. Planta Medica, 2007. 73(09): p. P_549.
14. Evangelou, A., et al., Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers. In vivo (Athens, Greece), 2000. 14(2): p. 363-366.
15. Esmaeili, M., The effect of ascorbic acid morphine withdrawal syndrome signs in rat. The Journal of Qazvin University of Medical Sciences, 2007. 10(4): p. 25-31.
16. Kosten, T.R. and T.P. George, The neurobiology of opioid dependence: implications for treatment. Science & practice perspectives, 2002. 1(1): p. 13.
17. Zeraati, F., M. Araghchian, and M.H. Farjoo, Ascorbic Acid interaction with analgesic effect of morphine and tramadol in mice. Anesthesiology and pain medicine, 2014. 4(3).
18. Sepulveda, M.J., et al., Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: an in vivo microdialysis study. Pharmacology Biochemistry and Behavior, 1998. 60(1): p. 255-262.
19. Langerman, L., et al., A method of reducing the opioid withdrawal intensity using progressively increasing doses of naloxone. Journal of pharmacological and toxicological methods, 1999. 42(3): p. 115-119.
20. Fritz, H., et al., Intravenous vitamin C and cancer: a systematic review. Integrative cancer therapies, 2014. 13(4): p. 280-300.
| Files | ||
| Issue | Vol 8, No 1 (Winter 2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jcr.v8i1.7154 | |
| Keywords | ||
| Addiction; Morphine; Withdrawal syndrome; Ascorbic acid. | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Farhadi Nasab A, Raoufi S, Bahrami N. Ascorbic acid effect on morphine withdrawal symptoms in rats. J Craniomaxillofac Res. 2021;8(1):29-34.
