Volume 29, Issue 1 (3-2026)
J Arak Uni Med Sci 2026, 29(1): 5-12 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Nanava Z, Hatami Nemati H, Ahmai H, Khakpay R. Study on Changes in the Expression of Histamine and Histamine N-Methyltransferase Genes in the Lumbar Spinal Cord of Male Rats during Methamphetamine Abuse and Buprenorphine Treatment. J Arak Uni Med Sci 2026; 29 (1) :5-12
URL: http://jams.arakmu.ac.ir/article-1-8046-en.html
URL: http://jams.arakmu.ac.ir/article-1-8046-en.html
1- MSc, Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
2- Associate Professor, Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
3- Assistant Professor, Department of Basic Sciences, Farhangian University, P.O. Box 14665- 889 Tehran, Iran ,hahmadi@cfu.ac.ir
2- Associate Professor, Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
3- Assistant Professor, Department of Basic Sciences, Farhangian University, P.O. Box 14665- 889 Tehran, Iran ,
Abstract: (639 Views)
Introduction: Methamphetamine is a powerful psychostimulant which has been significantly abused in recent years. Buprenorphine, a derivative of morphine alkaloids, is effective in treating opioid addiction.
Methods: This experimental study involved eight groups of seven male rats each. It examined the effects of a 5-day intraperitoneal injection of methamphetamine, buprenorphine, their interactions, and methamphetamine withdrawal on the expression of histamine and histamine N-methyltransferase genes in the lumbar spinal cord. The collected data were analyzed using One-way ANOVA.
Results: The intraperitoneal administration of 10 mg/kg of methamphetamine and 6 or 10 mg/kg of buprenorphine over five days did not change the expression levels of histamine or histamine N-methyltransferase genes in of male rats lumbar spinal cord. However, discontinuing methamphetamine led to an increase in the expression of both genes in this area (P < 0.01). Furthermore, when examining the interaction between the two drugs, it was found that the expression of histamine N-methyltransferase gene was significantly higher in the group receiving methamphetamine plus 10 mg/kg buprenorphine compared to the methamphetamine-only group (P < 0.01).
Conclusions: Based on the results of this study and the mechanisms proposed in previous studies, it seems that methamphetamine withdrawal and/or the use of buprenorphine as a possible therapeutic modality can lead to stabilization of physiological balance in central nervous system by temporarily increasing brain histamine, thus reducing the complications of methamphetamine abuse.
Methods: This experimental study involved eight groups of seven male rats each. It examined the effects of a 5-day intraperitoneal injection of methamphetamine, buprenorphine, their interactions, and methamphetamine withdrawal on the expression of histamine and histamine N-methyltransferase genes in the lumbar spinal cord. The collected data were analyzed using One-way ANOVA.
Results: The intraperitoneal administration of 10 mg/kg of methamphetamine and 6 or 10 mg/kg of buprenorphine over five days did not change the expression levels of histamine or histamine N-methyltransferase genes in of male rats lumbar spinal cord. However, discontinuing methamphetamine led to an increase in the expression of both genes in this area (P < 0.01). Furthermore, when examining the interaction between the two drugs, it was found that the expression of histamine N-methyltransferase gene was significantly higher in the group receiving methamphetamine plus 10 mg/kg buprenorphine compared to the methamphetamine-only group (P < 0.01).
Conclusions: Based on the results of this study and the mechanisms proposed in previous studies, it seems that methamphetamine withdrawal and/or the use of buprenorphine as a possible therapeutic modality can lead to stabilization of physiological balance in central nervous system by temporarily increasing brain histamine, thus reducing the complications of methamphetamine abuse.
References
1. Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev 2019;99(4):2115-40. pmid: 31507244 doi:10.1152/physrev 00014.2018.
2. Clark TP. The history and pharmacology of buprenorphine: New advances in cats. J Vet Pharmacol Ther. 2022;45:1-30. doi: 10.1111/jvp.13073.
3. Hamamoto DT, Rhodus NL. Methamphetamine abuse and dentistry. Oral Dis. 2008;15(1):27-37. pmid: 18992021 doi:10.1111/j.1601-0825.2008. 01459.x
4. Stitt D. Substance use and the nervous system. Neurol System Dis. 2023;29(3): 923-45. doi: 10.1212/CON.0000000000001234
5. Pierce R. C, Kalivas P. W. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev. 1997;25(2):192–216. pmid: 9403138 doi: 10.1016/s0165-0173(97)00021-0
6. Jones S.R, Gainetdinov R.R, Wightman R.M, Caron M.G. Mechanisms of amphetamine action revealed in mice lacking the dopamine transporter. J Neurosci. 1998;18(6):1979-86. pmid: 9482784 doi: 10.1523/JNEUROSCI.18-06-01979.1998
7. Hamel C, Corace K, Hersi M, Rice D, Willows M, Macpherson P, et al. Psychosocial and pharmacologic interventions for methamphetamine addiction: protocol for a scoping review of the literature. Syst Rev. 2020;9(1):245. pmid: 33099314 doi: 10.1186/s13643-020-01499-z
8. Gowing L, Ali R, White JM, Mbewe D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017;(2):CD002025. pmid: 28220474 doi: 10.1002/14651858.CD002025.pub5
9. Kletter GB, Padmanabhan V, Beitins IZ, Marshall JC, et al. Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys. J Clin Endocrinol Metab. 1997;82(12):4010-14. pmid: 9398704 doi: 10.1210/jcem.82.12.4458
10. Brabant C, Alleva L, Quertemont E, Tirelli E. Involvement of the brain histaminergic system in addiction and addiction-related behaviors: A comprehensive review with emphasis on the potential therapeutic use of histaminergic compounds in drug dependence. Prog Neurobiol. 2010;92(3):421-41. pmid: 20638439 doi: 10.1016/j.pneurobio.2010.07.002
11. Brown RE, Stevens DR, Haas HL. The physiology of brain histamine. Prog Neurobiol. 2001;63(6):637–72. pmid: 11164999 doi: 10.1016/s0301-0082(00)00039-3
12. Lin J, Dauvilliers Y, Arnulf I, Bastuji H, Anaclet C, Parmentier R, et al. An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients. Neurobiol Dis. 2008;30(1):74–83. pmid: 18295497 doi: 10.1016/j.nbd.2007.12.003
13. Horton JR, Sawada K, Nishibori M, Cheng X. Structural Basis for Inhibition of Histamine N-Methyltransferase by Diverse Drugs. J Mol Biol. 2005;353(2):334-44. pmid: 16168438 doi:10.1016/j.jmb.2005.08.040.
14. Oishi R, Baba M, Nishibori M, Itoh Y, Saeki K. Involvement of central histaminergic and cholinergic systems in the morphine-induced increase in blood-brain barrier permeability to sodium fluorescein in mice. Naunyn Schmiedebergs Arch Pharmacol. 1989;339(1-2):159-65. pmid: 2566923 doi: 10.1007/BF00165138.
15. Sanna MD, Borgonetti V, Masini E, Galeotti N. Histamine H4 receptor stimulation in the locus coeruleus attenuates neuropathic pain by promoting the coeruleospinal noradrenergic inhibitory pathway. Eur J Pharmac. 2020;868(5):172859. pmid: 31843515 doi: 10.1016/j.ejphar.2019.172859
16. Itoh Y, Nishibori M, Oishi R, Saeki K. Neuronal histamine inhibits methamphetamine-induced locomotor hyperactivity in mice. Neurosci Lett. 1984;48(3):305–9. pmid: 6541326 doi: 10.1016/0304-3940(84)90055-7
17. Watanabe T, Yanai K. Studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography. Tohoku J Exp Med. 2001;195:197–217. pmid: 11908822 doi: 10.1620/tjem.195.197
18. Asser A, Taba P. Psychostimulants and movement disorders. Front Neurol 2015;6:75. pmid: 25941511 doi: 10.3389/fneur. 2015.00075.
19. Schwelberger H.G. Histamine N-methyltransferase (HNMT) enzyme and gene. In Histamine N-methyltransferase[19-May-2026]. Available from: https://www.ncbi.nlm.nih.gov/gene/3176
20. Shahbazi R, Hatami Nemati H, Ahmadi H, Zogoulipour F. Nociceptive threshold response and alterations of special genes expression during methamphetamine administration and treatment with buprenorphine. J Basic Res Med Sci. 2022;9(2):25-34.
21. Tracy L, Hellem TL. A review of methamphetamine dependence and withdrawal treatment: a focus on anxiety outcomes. Journal of Subst Abuse Treat. 2016;71:16-22. pmid: 27776672 doi: 10.1016/j.jsat.2016.08.011
22. Ferrucci M, Pasquali L, Paparelli A, Ruggieri S, Fornai F. Pathways of Methamphetamine Toxicity. Ann N Y Acad Sci. 2008;1139:177-85. pmid: 18991862 doi: 10.1196/annals.1432.013
23. Nolan T, Hands R.E, Bustin S.A. Quantification of mRNA using real-time RT-PCR. Nat Protoc. 2006;1(3):1559-82. pmid: 17406449 doi: 10.1038/nprot.2006.236
24. Safdar M, Junejo Y. Development and validation of fast duplex real-time PCR assays based on SYBER Green florescence for detection of bovine and poultry origins in feedstuffs. Food Chem. 2015;173:660-4. pmid: 25466073 doi: 10.1016/j.foodchem.2014.10.088
25. Kitanaka N, Hall FS, Kobori S, Kushihara S.Oyama H, Sasaoka Y, et al. Metoprine, a histamine N-methyltransferase inhibitor, attenuates methamphetamine-induced hyperlocomotion via activation of histaminergic neurotransmission in mice. Pharmacol Biochem Behav. 2021;209:173257. pmid: 34418452 doi: 10.1016/j.pbb.2021.173257
26. Milesi-Hallé A, McMillan DE, Laurenzana EM, Byrnes-Blake KA, Owens SM. Sex differences in (+)-amphetamine- and (+)- methamphetamine-induced behavioral response in male and female Sprague–Dawley rats. Pharmacol Biochem Behav. 2007;86(1):140-9. pmid: 17275894 doi: 10.1016/j.pbb.2006.12.018
27. Thrash B, Karuppagounder SS, Uthayathas S, Suppiramaniam V, Dhanasekaran M. Neurotoxic effects of methamphetamine. Neuroch Res. 2010;35:171-9. pmid: 34186102 doi: 10.1016/j.expneurol.2021.113795
28. Ogawa S, Yanai K, Watanabe T, Wang ZM, Akaike H, Ito Y, et al. Histamine responses of large neostriatal interneurons in histamine H1 and H2 receptor knock-out mice. Brain Res Bull. 2009;16;78(4-5):189-94. pmid: 19063949 doi: 10.1016/j.brainresbull.2008.10.016.
29. Yoshikawa T, Nakamura T, Yanai K. Histamine N-Methyltransferase in the Brain. Int J Mol Sci .2019; 20(3):737. pmid: 30744146 doi: 10.3390/ijms20030737.
30. Blaney A, Jampachaisri K, Huss MK, Pacharinsak C. Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLoS One .2021;16(2):e0246213. pmid: 33534864 doi: 10.1371/journal. pone.0246213
31. Girotra S, Atray R, Mittal M. No cutaneous histamine release with buprenorphine? Acta Anaesthesiol Scand. 1990;34(4):301-3. pmid: 1693031 doi: 10.1111/j.1399-6576. 1990.tb03090. x.
32. Shintani S, Umezato M, Toba Y, Yamaji Y, Kitaura K, Tani T, et al. [Pharmacological properties of buprenorphine, a new analgesic agent. Part II. (author's transl)]. [in Japanese] Nihon Yakubutsugaku Zasshi. 1982;79(3):173-91. pmid: 6123475 doi: 10.1254/fpj.79.173.
33. Etaee F, Asadbegi M, Taslimi Z, Shahidi S, Sarihi A. The effects of methamphetamine and buprenorphine, and their interaction on anxiety-like behavior and locomotion in male rats. Neurosci Lett. 2017;655:172-8. pmid: 28698151 doi: 10.1016/j.neulet.2017.04.043
34. Kitanaka N, Kitanaka J, Tatsuta T, Tanaka K, Watabe K, Nishiyama N, et al. Withdrawal from fixed-dose injection of methamphetamine decreases cerebral levels of 3-methoxy-4-hydroxyphenylglycol and induces the expression of anxiety-related behavior in mice. Neurochem Res. 2010;35(5):749-60. pmid: 20148307 doi: 10.1007/s11064-010-0132-4
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
