Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice

  • Chan Lee (Department of Pharmacology, School of Medicine, Keimyung University) ;
  • Jung-Hee Jang (Department of Pharmacology, School of Medicine, Keimyung University) ;
  • Gyu Hwan Park (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2022.10.16
  • Accepted : 2023.01.09
  • Published : 2023.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF-2016R1A6A1A03011325; NRF-2022R1A2C1012031).

References

  1. Ares-Santos, S., Granado, N. and Moratalla, R. (2013) The role of dopamine receptors in the neurotoxicity of methamphetamine. J. Intern. Med. 273, 437-453. https://doi.org/10.1111/joim.12049
  2. Aydin, E., Turkez, H. and Geyikoglu, F. (2013) Antioxidative, anticancer and genotoxic properties of α-pinene on N2a neuroblastoma cells. Biologia 68, 1004-1009. https://doi.org/10.2478/s11756-013-0230-2
  3. Chen, Z. X. and Pervaiz, S. (2009) BCL-2: pro-or anti-oxidant? Front. Biosci. Elite Ed. 1, 263-268.
  4. Chomchai, C. and Chomchai, S. (2015) Global patterns of methamphetamine use. Curr. Opin. Psychiatry 28, 269-274. https://doi.org/10.1097/YCO.0000000000000168
  5. Gibb, J. and Kogan, F. (1979) Influence of dopamine synthesis on methamphetamine-induced changes in striatal and adrenal tyrosine hydroxylase activity. Naunyn Schmiedebergs Arch. Pharmacol. 310, 185-187. https://doi.org/10.1007/BF00500283
  6. Jayanthi, S., Daiwile, A. P. and Cadet, J. L. (2021) Neurotoxicity of methamphetamine: Main effects and mechanisms. Exp. Neurol. 344, 113795.
  7. Jayanthi, S., Deng, X., Bordelon, M., Mccoy, M. T. and Cadet, J. L. (2001) Methamphetamine causes differential regulation of prodeath and anti-death Bcl-2 genes in the mouse neocortex. FASEB J. 15, 1745-1752. https://doi.org/10.1096/fj.01-0025com
  8. Jayanthi, S., Deng, X., H. Noailles, P. A., Ladenheim, B. and Lud Cadet, J. (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J. 18, 238-251. https://doi.org/10.1096/fj.03-0295com
  9. Juan, C. A., Perez De La Lastra, J. M., Plou, F. J. and Perez-Lebena, E. (2021) The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci. 22, 4642.
  10. Jumnongprakhon, P., Govitrapong, P., Tocharus, C., Pinkaew, D. and Tocharus, J. (2015) Melatonin protects methamphetamine-induced neuroinflammation through NF-κB and Nrf2 pathways in glioma cell line. Neurochem. Res. 40, 1448-1456. https://doi.org/10.1007/s11064-015-1613-2
  11. Kim, B., Yun, J. and Park, B. (2020) Methamphetamine-induced neuronal damage: neurotoxicity and neuroinflammation. Biomol. Ther. (Seoul) 28, 381-388. https://doi.org/10.4062/biomolther.2020.044
  12. Kim, D.-S., Lee, H.-J., Jeon, Y.-D., Han, Y.-H., Kee, J.-Y., Kim, H.-J., Shin, H.-J., Kang, J., Lee, B. S., Kim, S.-H., Kim, S.-J., Park, S.-H., Choi, B.-M., Park, S.-J., Um, J.-Y. and Hong, S.-H. (2015) Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and the NF-κB pathway in mouse peritoneal macrophages. Am. J. Chin. Med. 43, 731-742. https://doi.org/10.1142/S0192415X15500457
  13. Kitamura, O., Takeichi, T., Wang, E. L., Tokunaga, I., Ishigami, A. and Kubo, S.-I. (2010) Microglial and astrocytic changes in the striatum of methamphetamine abusers. Leg. Med. 12, 57-62. https://doi.org/10.1016/j.legalmed.2009.11.001
  14. Lavoie, M. J., Card, J. P. and Hastings, T. G. (2004) Microglial activation precedes dopamine terminal pathology in methamphetamineinduced neurotoxicity. Exp. Neurol. 187, 47-57. https://doi.org/10.1016/j.expneurol.2004.01.010
  15. Loftis, J. M. and Janowsky, A. (2014) Neuroimmune basis of methamphetamine toxicity. Int. Rev. Neurobiol. 118, 165-197. https://doi.org/10.1016/B978-0-12-801284-0.00007-5
  16. Maragos, W. F., Jakel, R., Chesnut, D., Pocernich, C. B., Butterfield, D. A., St Clair, D. and Cass, W. A. (2000) Methamphetamine toxicity is attenuated in mice that overexpress human manganese superoxide dismutase. Brain Res. 878, 218-222. https://doi.org/10.1016/S0006-8993(00)02707-4
  17. Menezes, I. A., Barreto, C. M., Antoniolli, A. R., Santos, M. R. and De Sousa, D. P. (2010) Hypotensive activity of terpenes found in essential oils. Z. Naturforsch. C, J. Biosci. 65, 562-566. https://doi.org/10.1515/znc-2010-9-1005
  18. Nguyen, P.-T., Dang, D.-K., Tran, H.-Q., Shin, E.-J., Jeong, J. H., Nah, S.-Y., Cho, M. C., Lee, Y. S., Jang, C.-G. and Kim, H.-C. (2019) Methiopropamine, a methamphetamine analogue, produces neurotoxicity via dopamine receptors. Chem. Biol. Interact. 305, 134-147. https://doi.org/10.1016/j.cbi.2019.03.017
  19. Raisova, M., Hossini, A. M., Eberle, J., Riebeling, C., Orfanos, C. E., Geilen, C. C., Wieder, T., Sturm, I. and Daniel, P. T. (2001) The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J. Invest. Dermatol. 117, 333-340. https://doi.org/10.1046/j.0022-202x.2001.01409.x
  20. Riddle, E. L., Fleckenstein, A. E. and Hanson, G. R. (2006) Mechanisms of methamphetamine-induced dopaminergic neurotoxicity. AAPS J. 8, E413-E418. https://doi.org/10.1007/BF02854914
  21. Rivera-Yanez, C. R., Terrazas, L. I., Jimenez-Estrada, M., Campos, J. E., Flores-Ortiz, C. M., Hernandez, L. B., Cruz-Sanchez, T., Garrido-Farina, G. I., Rodriguez-Monroy, M. A. and Canales-Martinez, M. M. (2017) Anti-Candida activity of Bursera morelensis Ramirez essential oil and two compounds, α-pinene and γ-terpinene-an in vitro study. Molecules 22, 2095.
  22. Satou, T., Kasuya, H., Maeda, K. and Koike, K. (2014) Daily inhalation of α-pinene in mice: effects on behavior and organ accumulation. Phytother. Res. 28, 1284-1287. https://doi.org/10.1002/ptr.5105
  23. Shin, E.-J., Shin, S. W., Nguyen, T.-T. L., Park, D. H., Wie, M.-B., Jang, C.-G., Nah, S.-Y., Yang, B. W., Ko, S. K., Nabeshima, T. and Kim, H. C. (2014) Ginsenoside Re rescues methamphetamine-induced oxidative damage, mitochondrial dysfunction, microglial activation, and dopaminergic degeneration by inhibiting the protein kinase Cδ gene. Mol. Neurobiol. 49, 1400-1421. https://doi.org/10.1007/s12035-013-8617-1
  24. Thomas, D. M., Walker, P. D., Benjamins, J. A., Geddes, T. J. and Kuhn, D. M. (2004) Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J. Pharmacol. Exp. Ther. 311, 1-7. https://doi.org/10.1124/jpet.104.070961
  25. Tulloch, I., Afanador, L., Mexhitaj, I., Ghazaryan, N., Garzagongora, A. G. and Angulo, J. A. (2011) A single high dose of methamphetamine induces apoptotic and necrotic striatal cell loss lasting up to 3 months in mice. Neuroscience 193, 162-169. https://doi.org/10.1016/j.neuroscience.2011.07.020
  26. Veerasakul, S., Thanoi, S., Watiktinkorn, P., Reynolds, G. P. and Nudmamud-Thanoi, S. (2016) Does elevated peripheral benzodiazepine receptor gene expression relate to cognitive deficits in methamphetamine dependence? Hum. Psychopharmacol. 31, 243-246. https://doi.org/10.1002/hup.2523
  27. Volkow, N. D., Chang, L., Wang, G.-J., Fowler, J. S., Ding, Y.-S., Sedler, M., Logan, J., Franceschi, D., Gatley, J., Hitzemann, R., Gifford, A., Wong, C. and Pappas, N. (2001a) Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am. J. Psychiatry 158, 2015-2021. https://doi.org/10.1176/appi.ajp.158.12.2015
  28. Volkow, N. D., Chang, L., Wang, G.-J., Fowler, J. S., Leonido-Yee, M., Franceschi, D., Sedler, M. J., Gatley, S. J., Hitzemann, R., Ding, Y.-S., Logan, J., Wong, C. and Miller, E. N. (2001b) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am. J. Psychiatry 158, 377-382. https://doi.org/10.1176/appi.ajp.158.3.377
  29. Volz, T. J., Fleckenstein, A. E. and Hanson, G. R. (2007a) Methamphetamine-induced alterations in monoamine transport: implications for neurotoxicity, neuroprotection and treatment. Addiction 102, 44-48. https://doi.org/10.1111/j.1360-0443.2007.01771.x
  30. Volz, T. J., Hanson, G. R. and Fleckenstein, A. E. (2007b) The role of the plasmalemmal dopamine and vesicular monoamine transporters in methamphetamine-induced dopaminergic deficits. J. Neurochem. 101, 883-888. https://doi.org/10.1111/j.1471-4159.2006.04419.x
  31. Yang, H., Woo, J., Pae, A. N., Um, M. Y., Cho, N.-C., Park, K. D., Yoon, M., Kim, J., Lee, C. J. and Cho, S. (2016) α-Pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAA-benzodiazepine receptors. Mol. Pharmacol. 90, 530-539. https://doi.org/10.1124/mol.116.105080
  32. Yang, X., Wang, Y., Li, Q., Zhong, Y., Chen, L., Du, Y., He, J., Liao, L., Xiong, K., Yi, C.-X. and Yan, J. (2018) The main molecular mechanisms underlying methamphetamine-induced neurotoxicity and implications for pharmacological treatment. Front. Mol. Neurosci. 11, 186.
  33. Younus, H. (2018) Therapeutic potentials of superoxide dismutase. Int. J. Health Sci. (Qassim) 12, 88-93.