The effects of morphine administration on the central nervous system (CNS): advantages and disadvantages

Authors

  • Arezou Mehrabi School of Medicine, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
  • Bahareh Lashtoo Aghaee Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran
  • Samaneh Farrokhfar Department of anatomical sciences, Faculty of Medicine, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran

DOI:

https://doi.org/10.31117/neuroscirn.v7i2.348

Keywords:

Morphine, CNS, Opioid, Pain management, Preclinical studies, Neurological impairments

Abstract

Morphine, a potent opioid analgesic, plays a critical role in pain management but elicits complex effects on the central nervous system (CNS), demonstrating both beneficial and detrimental outcomes. This paper reviews preclinical studies to examine morphine's interactions with the CNS, notably via binding to opioid receptors, leading to analgesia as well as a series of adverse effects, including addiction, tolerance, and neurological impairments. Acute exposure to morphine alters neurotransmitter activity, gene expression, and neuronal firing rates. In contrast, chronic use results in significant neuronal damage, altered memory functions, increased pain sensitivity, and neuroinflammation, highlighting the drug's impact on neurogenesis and neural cell viability. Additionally, morphine's protective properties against neurotoxic insults are discussed, alongside its potential to disrupt cellular and molecular pathways, culminating in neurotoxicity and cognitive deficits. Given the dual nature of morphine's impact on the CNS - protective vs. harmful, depending on specific conditions such as dosage, disease type, and administration frequency - this paper underscores the necessity for further research to untangle this complex interplay to leverage morphine's pain management benefits while minimizing its risks. A thorough evaluation of morphine administration practices can help reconcile these conflicting results.

References

Abdyazdani, N., Nourazarian, A., Nozad Charoudeh, H., Kazemi, M., Feizy, N., Akbarzade, M., Mehdizadeh, A., Rezaie, J., & Rahbarghazi, R. (2017). The role of morphine on rat neural stem cells viability, neuro-angiogenesis and neuro-steroidgenesis properties. Neuroscience Letters, 636, 205–212. https://doi.org/10.1016/J.NEULET.2016.11.025

Aceves, M., Terminel, M. N., Okoreeh, A., Aceves, A. R., Gong, Y. M., Polanco, A., Sohrabji, F., & Hook, M. A. (2019). Morphine increases macrophages at the lesion site following spinal cord injury: Protective effects of minocycline. Brain, Behavior, and Immunity, 79, 125–138. https://doi.org/10.1016/J.BBI.2019.01.023

Ali, S. F., Toshitaka, N. & Tomoji, Y. (2004). Current status of drug dependence/abuse studies : cellular and molecular mechanisms of drugs of abuse and neurotoxicity. New York Academy of Sciences.

Amini, K., Zhaleh, H., Tahvilian, R., & Farnia, V. (2019). Low concentration of morphine protects against cell death, oxidative stress and calcium accumulation by nicotine in PC12 cells. Bratislavske Lekarske Listy, 120(4), 256–262. https://doi.org/10.4149/BLL_2019_042

Anghel, A., Jamieson, C. A. M., Ren, X., Young, J., Porche, R., Ozigbo, E., Ghods, D. E., Lee, M. L., Liu, Y., Lutfy, K., & Friedman, T. C. (2010). Gene expression profiling following short-term and long-term morphine exposure in mice uncovers genes involved in food intake. Neuroscience, 167(2), 554. https://doi.org/10.1016/J.NEUROSCIENCE.2010.01.043

Arabian, M., Aboutaleb, N., Soleimani, M., Ajami, M., Habibey, R., & Pazoki-Toroudi, H. (2018). Activation of mitochondrial KATP channels mediates neuroprotection induced by chronic morphine preconditioning in hippocampal CA-1 neurons following cerebral ischemia. Advances in Medical Sciences, 63(2), 213–219. https://doi.org/10.1016/J.ADVMS.2017.11.003

Arabian, M., Aboutaleb, N., Soleimani, M., Ajami, M., Habibey, R., Rezaei, Y., & Pazoki-Toroudi, H. (2018). Preconditioning with morphine protects hippocampal CA1 neurons from ischemia–reperfusion injury via activation of the mTOR pathway. Canadian Journal of Physiology and Pharmacology, 96(1), 80–87. https://doi.org/10.1139/cjpp-2017-0245

Arabian, M., Aboutaleb, N., Soleimani, M., Mehrjerdi, F. Z., Ajami, M., & Pazoki-Toroudi, H. (2015). Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice. Iranian Journal of Basic Medical Sciences, 18(1), 14.

Assunção-Silva, R. C., Gomes, E. D., Sousa, N., Silva, N. A., & Salgado, A. J. (2015). Hydrogels and Cell Based Therapies in Spinal Cord Injury Regeneration. Stem Cells International, 2015. https://doi.org/10.1155/2015/948040

Asuni, G. P., Speidell, A., & Mocchetti, I. (2021). Neuronal apoptosis induced by morphine withdrawal is mediated by the p75 neurotrophin receptor. Journal of Neurochemistry, 158(2), 169–181. https://doi.org/10.1111/JNC.15355

Atici, S., Cinel, L., Cinel, I., Doruk, N., Aktekin, M., Akca, A., Camdeviren, H., & Oral, U. (2004). Opioid neurotoxicity: comparison of morphine and tramadol in an experimental rat model. The International Journal of Neuroscience, 114(8), 1001–1011. https://doi.org/10.1080/00207450490461314

Avelar, A. J., Cooper, S. Y., Wright, T. D., Wright, S. K., Richardson, M. R., & Henderson, B. J. (2022). Morphine Exposure Reduces Nicotine-Induced Upregulation of Nicotinic Receptors and Decreases Volitional Nicotine Intake in a Mouse Model. Nicotine & Tobacco Research, 24(8), 1161. https://doi.org/10.1093/NTR/NTAC002

Barrow, T. M., Byun, H. M., Li, X., Smart, C., Wang, Y. X., Zhang, Y., Baccarelli, A. A., & Guo, L. (2017). The effect of morphine upon DNA methylation in ten regions of the rat brain. Epigenetics, 12(12), 1038–1047. https://doi.org/10.1080/15592294.2017.1398296

Bian, Y., Wang, X., Liang, J. hui, Li, L., Wu, X., Tang, B., Leung, G. P. H., & Lee, S. M. Y. (2022). The development of behavioral sensitization induced by a single morphine exposure in adult zebrafish (Danio rerio). Progress in Neuro-psychopharmacology & Biological Psychiatry, 113. https://doi.org/10.1016/J.PNPBP.2021.110456

Cansız, D., Ustundag, U. V., Unal, I., Alturfan, A. A., & Emekli-Alturfan, E. (2022). Morphine attenuates neurotoxic effects of MPTP in zebrafish embryos by regulating oxidant/antioxidant balance and acetylcholinesterase activity. Drug and Chemical Toxicology, 45(6), 2439–2447. https://doi.org/10.1080/01480545.2021.1957558

Cao, Q., Benton, R. L., & Whittemore, S. R. (2002). Stem cell repair of central nervous system injury. Journal of Neuroscience Research, 68(5), 501–510. https://doi.org/10.1002/JNR.10240

Chahkandi, M., Askari Phd, N., & Asadikaram, G. (2015). The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats. Addiction & Health, 7(3–4), 130.

Chambers, R. A. (2013). Adult Hippocampal Neurogenesis in the Pathogenesis of Addiction and Dual Diagnosis Disorders. Drug and Alcohol Dependence, 130(0), 1. https://doi.org/10.1016/J.DRUGALCDEP.2012.12.005

Chen, K., Phan, T., Lin, A., Sardo, L., Mele, A. R., Nonnemacher, M. R., & Klase, Z. (2020). Morphine exposure exacerbates HIV-1 Tat driven changes to neuroinflammatory factors in cultured astrocytes. PLOS ONE, 15(3), e0230563. https://doi.org/10.1371/JOURNAL.PONE.0230563

Chen, Q., Cui, J., Zhang, Y., & Yu, L. C. (2008). Prolonged morphine application modulates Bax and Hsp70 levels in primary rat neurons. Neuroscience Letters, 441(3), 311–314. https://doi.org/10.1016/J.NEULET.2008.06.067

Chen, Y., Wang, X., Xiao, M., Kang, N., Zeng, W., & Zhang, J. (2022). Prenatal morphine exposure increases gamma oscillation and theta coherence in the rat reward system. Neurotoxicology, 90, 246–255. https://doi.org/10.1016/J.NEURO.2022.04.007

Cichewicz, D. L., Haller, V. L., & Welch, S. P. (2001). Changes in Opioid and Cannabinoid Receptor Protein following Short-Term Combination Treatment with Δ9-Tetrahydrocannabinol and Morphine. Journal of Pharmacology and Experimental Therapeutics, 297(1), 121–127.

Cui, J., Chen, Q., Yu, L. C., & Zhang, Y. (2008). Chronic morphine application is protective against cell death in primary human neurons. Neuroreport, 19(18), 1745–1749. https://doi.org/10.1097/WNR.0B013E3283186FD7

Cunha-Oliveira, T., Silva, L., Silva, A. M., Moreno, A. J., Oliveira, C. R., & Santos, M. S. (2013). Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria. Toxicology Letters, 219(3), 298–306. https://doi.org/10.1016/J.TOXLET.2013.03.025

Darvishi, F. Z., & Saadat, M. (2022). Morphine may have a role in telomere shortening. Psychiatric Genetics, 32(2), 87–89. https://doi.org/10.1097/YPG.0000000000000311

Dholakiya, S. L., Aliberti, A., & Barile, F. A. (2016). Morphine sulfate concomitantly decreases neuronal differentiation and opioid receptor expression in mouse embryonic stem cells. Toxicology Letters, 247, 45–55. https://doi.org/10.1016/J.TOXLET.2016.01.010

Ding, H., Kiguchi, N., Mabry, K. M., Kishioka, S., & Ko, M. C. (2023). Functional consequences of short-term exposure to opioids versus cannabinoids in nonhuman primates. Neuropharmacology, 223. https://doi.org/10.1016/J.NEUROPHARM.2022.109328

Dominguez, J. E., & Habib, A. S. (2013). Prophylaxis and treatment of the side-effects of neuraxial morphine analgesia following cesarean delivery. Current Opinion in Anaesthesiology, 26(3), 288–295. https://doi.org/10.1097/ACO.0B013E328360B086

Doyle, T., Bryant, L., Batinic-Haberle, I., Little, J., Cuzzocrea, S., Masini, E., Spasojevic, I., & Salvemini, D. (2009). Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance. Neuroscience, 164(2), 702–710. https://doi.org/10.1016/J.NEUROSCIENCE.2009.07.019

Drastichova, Z., Hejnova, L., Moravcova, R., & Novotny, J. (2021). Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine. Life (Basel, Switzerland), 11(7), 683. https://doi.org/10.3390/LIFE11070683

Eftekhar-Vaghefi, S. H., Asadi-Shekaari, M., & Esmaeili-Mahani, S. (2019). Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells. International Journal of Neuroscience, 129(2), 129–138. https://doi.org/10.1080/00207454.2018.1494169

Eisch, A. J., Barrot, M., Schad, C. A., Self, D. W., & Nestler, E. J. (2000). Opiates inhibit neurogenesis in the adult rat hippocampus. Proceedings of the national academy of sciences of the United States of America (PNAS), 97(13), 7579–7584. https://doi.org/10.1073/pnas.120552597

Eisch, A.J. & Mandyam, C.D. (2007). Adult neurogenesis: can analysis of cell cycle proteins move us “Beyond BrdU”? Current Pharmaceutical Biotechnology, 8(3), 147–165. https://doi.org/10.2174/138920107780906540

Elyasi, L., Eftekhar-Vaghefi, S. H., & Esmaeili-Mahani, S. (2014). Morphine protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cell damage: involvement of anti-oxidant, calcium blocking, and anti-apoptotic properties. Rejuvenation Research, 17(3), 255–263. https://doi.org/10.1089/REJ.2013.1473

Espinosa, V. P., Liu, Y., Ferrini, M., Anghel, A., Nie, Y., Tripathi, P. V., Porche, R., Jansen, E., Stuart, R. C., Nillni, E. A., Lutfy, K., & Friedman, T. C. (2008). Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the “switch” to opiate addiction. Neuroscience, 156(3), 788–799. https://doi.org/10.1016/J.NEUROSCIENCE.2008.07.063

Famitafreshi, H., Karimian, M., & Marefati, N. (2015). Long-term morphine addiction reduces neurogenesis and memory performance and alters emotional reactivity and anxiety levels in male rats. Open Access Animal Physiology, 7, 129–136. https://doi.org/10.2147/OAAP.S87674

Fan, W., Wang, H., Zhang, Y., Loh, H. H., Law, P. Y., & Xu, C. (2018). Morphine regulates adult neurogenesis and contextual memory extinction via the PKCε/Prox1 pathway. Neuropharmacology, 141, 126–138. https://doi.org/10.1016/J.NEUROPHARM.2018.08.031

Farahani, F., Pachenari, N., Mohammad Ahmadi-Soleimani, S., Azizi, H., & Semnanian, S. (2023). Acute morphine injection persistently affects the electrophysiological characteristics of rat locus coeruleus neurons. Neuroscience Letters, 795. https://doi.org/10.1016/J.NEULET.2023.137048

Farrokhfar, S., Tiraihi, T., Movahedin, M., & Azizi, H. (2020). Differential gene expression by lithium chloride induction of adipose-derived stem cells into neural phenotype cells. Iranian Journal of Basic Medical Sciences, 23(4), 544. https://doi.org/10.22038/IJBMS.2020.41582.9820

Feizy, N., Nourazarian, A., Rahbarghazi, R., Nozad Charoudeh, H., Abdyazdani, N., Montazersaheb, S., & Narimani, M. (2016). Morphine Inhibited the Rat Neural Stem Cell Proliferation Rate by Increasing Neuro Steroid Genesis. Neurochemical Research, 41(6), 1410–1419. https://doi.org/10.1007/S11064-016-1847-7

Feng, Y., Lu, Y., Lin, X., Gao, Y., Zhao, Q., Li, W., & Wang, R. (2008). Endomorphins and morphine limit anoxia-reoxygenation-induced brain mitochondrial dysfunction in the mouse. Life Sciences, 82(13–14), 752–763. https://doi.org/10.1016/J.LFS.2008.01.004

Fischer, S. J., Arguello, A. A., Charlton, J. J., Fuller, D. C., Zachariou, V., & Eisch, A. J. (2008). Morphine blood levels, dependence, and regulation of hippocampal subgranular zone proliferation rely on administration paradigm. Neuroscience, 151(4), 1217–1224. https://doi.org/10.1016/J.NEUROSCIENCE.2007.11.035

Fukuda, T., Chidambaran, V., Mizuno, T., Venkatasubramanian, R., Ngamprasertwong, P., Olbrecht, V., Esslinger, H. R., Vinks, A. A., & Sadhasivam, S. (2013). OCT1 genetic variants influence the pharmacokinetics of morphine in children. Pharmacogenomics, 14(10), 1141–1151. https://doi.org/10.2217/PGS.13.94

Fürst, Z., Riba, P., & Al-Khrasani, M. (2013). New approach to the neurobiological mechanisms of addiction - PubMed. Neuropsychopharmacologia Hungarica, 15(4), 189–205. https://pubmed.ncbi.nlm.nih.gov/24380960/

Gabel, F., Hovhannisyan, V., Berkati, A. K., & Goumon, Y. (2022). Morphine-3-Glucuronide, Physiology and Behavior. Frontiers in Molecular Neuroscience, 15. https://doi.org/10.3389/FNMOL.2022.882443

Gach, K., Wyrębska, A., Fichna, J., & Janecka, A. (2011). The role of morphine in regulation of cancer cell growth. Naunyn-schmiedeberg’s Archives of Pharmacology, 384(3), 221. https://doi.org/10.1007/S00210-011-0672-4

Glare, P. A., & Walsh, T. D. (1991). Clinical pharmacokinetics of morphine. Therapeutic Drug Monitoring, 13(1), 1–23. https://doi.org/10.1097/00007691-199101000-00001

Guan, S., Jin, T., Han, S., Fan, W., Chu, H., & Liang, Y. (2021). Dihydroartemisinin alleviates morphine-induced neuroinflammation in BV-2 cells. Bioengineered, 12(2), 9401. https://doi.org/10.1080/21655979.2021.1982311

Harburg, G. C., Hall, F. S., Harrist, A. V., Sora, I., Uhl, G. R., & Eisch, A. J. (2007). Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons. Neuroscience, 144(1), 77. https://doi.org/10.1016/J.NEUROSCIENCE.2006.09.018

Hauser K F, & Mangoura D. (1998). Diversity of the endogenous opioid system in development. Novel signal transduction translates multiple extracellular signals into neural cell growth and differentiation. Perspectives on Developmental Neurobiology, 5(4), 437–449.

Holmes, M. M., & Galea, L. A. M. (2002). Defensive behavior and hippocampal cell proliferation: Differential modulation by naltrexone during stress. Behavioral Neuroscience, 116(1), 160–168. https://doi.org/10.1037/0735-7044.116.1.160

Jaferi, A., Lane, D. A., & Pickel, V. M. (2009). Subcellular plasticity of the corticotropin-releasing factor receptor in dendrites of the mouse bed nucleus of the stria terminalis following chronic opiate exposure. Neuroscience, 163(1), 143–154. https://doi.org/10.1016/J.NEUROSCIENCE.2009.06.029

Jahanian, F., Hosseininejad, S. M., Ahidashti, H. A., Bozorgi, F., Khatir, I. G., Montazar, S. H., & Azarfar, V. (2018). Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial. Bulletin of Emergency & Trauma, 6(1), 31. https://doi.org/10.29252/BEAT-060105

Jahanshahi, M., Shabani, R., Nikmahzar, E., & Babakordi, F. (2014). Female Rat Hippocampal Cell Density after Conditioned Place Preference. Folia Biologica, 60(1), 47–51.

Jiang, C., Wang, X., Le, Q., Liu, P., Liu, C., Wang, Z., He, G., Zheng, P., Wang, F., & Ma, L. (2021). Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward. Molecular Psychiatry, 26(4), 1178–1193. https://doi.org/10.1038/S41380-019-0480-7

Jimenez-Gonzalez, A., García-Concejo, A., León-Lobera, F., & Rodriguez, R. E. (2018). Morphine delays neural stem cells differentiation by facilitating Nestin overexpression. Biochimica Et Biophysica Acta, 1862(3), 474–484. https://doi.org/10.1016/J.BBAGEN.2017.10.016

Jin, C., Araki, H., Nagata, M., Suemaru, K., Shibata, K., Kawasaki, H., Hamamura, T., & Gomita, Y. (2004). Withdrawal-induced c-Fos expression in the rat centromedial amygdala 24 h following a single morphine exposure. Psychopharmacology, 175(4), 428–435. https://doi.org/10.1007/S00213-004-1844-4

Kahn, L., Alonso, G., Normand, E., & Manzoni, O. J. (2005). Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus. The European Journal of Neuroscience, 21(2), 493–500. https://doi.org/10.1111/J.1460-9568.2005.03883.X

Kashiwagi, Y., Yi, H., Liu, S., Takahashi, K., Hayashi, K., Ikegami, D., Zhu, X., Gu, J., & Hao, S. (2021). Mitochondrial biogenesis factor PGC-1α suppresses spinal morphine tolerance by reducing mitochondrial superoxide. Experimental Neurology, 339. https://doi.org/10.1016/J.EXPNEUROL.2021.113622

Kennedy, B. K., & Lamming, D. W. (2016). The mechanistic Target of Rapamycin: The grand conducTOR of metabolism and aging. Cell Metabolism, 23(6), 990. https://doi.org/10.1016/J.CMET.2016.05.009

Khani, F., Pourmotabbed, A., Hosseinmardi, N., Nedaei, S. E., Fathollahi, Y., & Azizi, H. (2022). Impairment of spatial memory and dorsal hippocampal synaptic plasticity in adulthood due to adolescent morphine exposure. Progress in Neuro-psychopharmacology & Biological Psychiatry, 116, 110532. https://doi.org/10.1016/J.PNPBP.2022.110532

Khazali, H., & Mahmoudi, F. (2019). Morphine and kisspeptin influences on 5-α reductase and aromatase gene expression in adult male rats. Iranian Journal of Basic Medical sciences, 22(12), 1462. https://doi.org/10.22038/IJBMS.2019.14053

Kong, H., Jiang, C. Y., Hu, L., Teng, P., Zhang, Y., Pan, X. X., Sun, X. Di, & Liu, W. T. (2019). Morphine induces dysfunction of PINK1/Parkin-mediated mitophagy in spinal cord neurons implying involvement in antinociceptive tolerance. Journal of Molecular Cell Biology, 11(12), 1056–1068. https://doi.org/10.1093/JMCB/MJZ002

Konno, F., & Takayanagi, I. (1982). Effect of morphine on the stimuli-induced calcium uptake into synaptosomes isolated from morphine-tolerant rats. Japanese Journal of Pharmacology, 32(4), 625–632. https://doi.org/10.1254/JJP.32.625

Kupnicka, P., Kojder, K., Metryka, E., Kapczuk, P., Jeżewski, D., Gutowska, I., Goschorska, M., Chlubek, D., & Baranowska-Bosiacka, I. (2020). Morphine-element interactions - The influence of selected chemical elements on neural pathways associated with addiction. Journal of Trace Elements in Medicine and Biology, 60, 126495. https://doi.org/10.1016/J.JTEMB.2020.126495

Lapierre, J., Karuppan, M. K. M., Perry, M., Rodriguez, M., & El-Hage, N. (2021). Different Roles of Beclin1 in the Interaction Between Glia and Neurons after Exposure to Morphine and the HIV-Trans-Activator of Transcription (Tat) Protein. Journal of Neuroimmune Pharmacology, 17(3), 470–486. https://doi.org/10.1007/S11481-021-10017-4

Li, W. W., Irvine, K. A., Sahbaie, P., Guo, T. Z., Shi, X. Y., Tawfik, V. L., Kingery, W. S., & Clark, J. D. (2019). Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice. Anesthesiology, 130(2), 292–308. https://doi.org/10.1097/ALN.0000000000002495

Li, Z., Liu, J., Dong, F., Chang, N., Huang, R., Xia, M., Patterson, T. A., & Hong, H. (2023). Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor. International Journal of Molecular Sciences, 24(8). https://doi.org/10.3390/IJMS24087042

Lim, Y. J., Zheng, S., & Zuo, Z. (2004). Morphine preconditions Purkinje cells against cell death under in vitro simulated ischemia-reperfusion conditions. Anesthesiology, 100(3), 562–568. https://doi.org/10.1097/00000542-200403000-00015

Liu, Y., Lu, G. Y., Chen, W. Q., Li, Y. F., Wu, N., & Li, J. (2018). Agmatine inhibits chronic morphine exposure-induced impairment of hippocampal neural progenitor proliferation in adult rats. European Journal of Pharmacology, 818, 50–56. https://doi.org/10.1016/J.EJPHAR.2017.10.018

Lu, G., Zhou, Q. X., Kang, S., Li, Q. L., Zhao, L. C., Chen, J. D., Sun, J. F., Cao, J., Wang, Y. J., Chen, J., Chen, X. Y., Zhong, D. F., Chi, Z. Q., Xu, L., & Liu, J. G. (2010). Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A1 Receptors. The Journal of Neuroscience, 30(14), 5058. https://doi.org/10.1523/JNEUROSCI.0148-10.2010

Lyu, N., & Li, X. (2022). Effect of Exosomal Protein Expression and Electrochemical Nano Interface in Morphine Analgesia Tolerance. Cellular and Molecular Biology, 67(6), 40–47. https://pubmed.ncbi.nlm.nih.gov/35818216/

Mandyam, C. D., Norris, R. D., & Eisch, A. J. (2004). Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone. Journal of Neuroscience Research, 76(6), 783–794. https://doi.org/10.1002/JNR.20090

Meng, F., Li, Y., Chi, W., & Li, J. (2016). Morphine Preconditioning Downregulates MicroRNA-134 Expression Against Oxygen-Glucose Deprivation Injuries in Cultured Neurons of Mice. Journal of Neurosurgical Anesthesiology, 28(3), 195–202. https://doi.org/10.1097/ANA.0000000000000204

Muchhala, K. H., Jacob, J. C., Dewey, W. L., & Akbarali, H. I. (2021). Role of β-arrestin-2 in short- and long-term opioid tolerance in the dorsal root ganglia. European Journal of Pharmacology, 899, 174007. https://doi.org/10.1016/J.EJPHAR.2021.174007

Murphy, E. J. (2005). Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesthesia and Intensive Care, 33(3), 311–322. https://doi.org/10.1177/0310057X0503300306

Naderi, J., Samani, F., Amooheidari, A., Javanmard, S. H., Vahabzadeh, G., & Vaseghi, G. (2019). Evaluation of effects of morphine and ionizing radiation in cancer cell lines. Journal of Cancer Research and Therapeutics, 15(8), S144–S152. https://doi.org/10.4103/JCRT.JCRT_48_17

Nestler, E. J. (2001). Molecular basis of long-term plasticity underlying addiction. Nature Reviews Neuroscience 2001 2:2, 2(2), 119–128. https://doi.org/10.1038/35053570

Nowycky, M. C., Walters, J. R., & Roth, R. H. (1978). Dopaminergic neurons: effect of acute and chronic morphine administration on single cell activity and transmitter metabolism. Journal of Neural Transmission, 42(2), 99–116. https://doi.org/10.1007/BF01675349

Nyberg, F. (2009). The Role of the Somatotrophic Axis in Neuroprotection and Neuroregeneration of the Addictive Brain. International review of neurobiology, 88(C), 399–427. https://doi.org/10.1016/S0074-7742(09)88014-8

Nylander, E., Zelleroth, S., Nyberg, F., Grönbladh, A., & Hallberg, M. (2021). The effects of morphine, methadone, and fentanyl on mitochondria: A live cell imaging study. Brain Research Bulletin, 171, 126–134. https://doi.org/10.1016/J.BRAINRESBULL.2021.03.009

Ofoegbu, A., & B. Ettienne, E. (2021). Pharmacogenomics and Morphine. Journal of Clinical Pharmacology, 61(9), 1149–1155. https://doi.org/10.1002/JCPH.1873

Osmanlıoğlu, H. Ö., Yıldırım, M. K., Akyuva, Y., Yıldızhan, K., & Nazıroğlu, M. (2020). Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus. Molecular Neurobiology, 57(8), 3376–3389. https://doi.org/10.1007/S12035-020-01975-6

Parrott, A. C. (2018). Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs. Brain Sciences, 8(3). https://doi.org/10.3390/BRAINSCI8030043

Pirnik Z, Schwendt M, & Jezova D. (2001). Single dose of morphine influences plasma corticosterone and gene expression of main NMDA receptor subunit in the adrenal gland but not in the hippocampus. Endocrine Regulations, 35(4), 187–193.

Qian, L., Tan, K. S., Wei, S.-J., Wu, H.-M., Xu, Z., Wilson, B., Lu, R.-B., Hong, J.-S., & Flood, P. M. (2007). Microglia-mediated neurotoxicity is inhibited by morphine through an opioid receptor-independent reduction of NADPH oxidase activity. Journal of Immunology, 179(2), 1198–1209. https://doi.org/10.4049/JIMMUNOL.179.2.1198

Rahimi, S., Dadfar, B., Tavakolian, G., Asadi Rad, A., Rashid Shabkahi, A., & Siahposht-Khachaki, A. (2021). Morphine attenuates neuroinflammation and blood-brain barrier disruption following traumatic brain injury through the opioidergic system. Brain Research Bulletin, 176, 103–111. https://doi.org/10.1016/J.BRAINRESBULL.2021.08.010

Reymond, S., Vujić, T., Schvartz, D., & Sanchez, J. C. (2022). Morphine-induced modulation of Nrf2-antioxidant response element signaling pathway in primary human brain microvascular endothelial cells. Scientific Reports, 12(1), 1–10. https://doi.org/10.1038/s41598-022-08712-0

Roch, C., & van Oorschot, B. (2020). Opioidrotation bei Tumorschmerzen. Im Fokus Onkologie, 23(1), 19–21. https://doi.org/10.1007/S15015-019-0745-7

Rouhani, F., Khodarahmi, P., & Naseh, V. (2019). NGF, BDNF and Arc mRNA Expression in the Hippocampus of Rats After Administration of Morphine. Neurochemical Research, 44(9), 2139–2146. https://doi.org/10.1007/S11064-019-02851-Z

Rueda-Ruzafa, L., Cruz, F., Cardona, D., Hone, A. J., Molina-Torres, G., Sánchez-Labraca, N., & Roman, P. (2020). Opioid system influences gut-brain axis: Dysbiosis and related alterations. Pharmacological Research, 159, 104928. https://doi.org/10.1016/J.PHRS.2020.104928

Sakurada, T., Komatsu, T., & Sakurada, S. (2005). Mechanisms of nociception evoked by intrathecal high-dose morphine. Neurotoxicology, 26(5), 801–809. https://doi.org/10.1016/J.NEURO.2004.12.011

Sargeant, T. J., Miller, J. H., & Day, D. J. (2008). Opioidergic regulation of astroglial/neuronal proliferation: where are we now? Journal of neurochemistry, 107(4), 883–897. https://doi.org/10.1111/J.1471-4159.2008.05671.X

Schroeder, C. I., & Lewis, R. J. (2006). ω-Conotoxins GVIA, MVIIA and CVID: SAR and Clinical Potential. Marine Drugs, 4(3), 193.

Schuster, M., Bayer, O., Heid, F., & Laufenberg-Feldmann, R. (2018). Opioid rotation in cancer pain treatment - A systematic review. Deutsches Arzteblatt International, 115(9), 135–142. https://doi.org/10.3238/ARZTEBL.2018.0135

Soto-Montenegro, M. aL, García-Vázquez, V., Lamanna-Rama, N., López-Montoya, G., Desco, M., & Ambrosio, E. (2022). Neuroimaging reveals distinct brain glucose metabolism patterns associated with morphine consumption in Lewis and Fischer 344 rat strains. Scientific Reports, 12(1). https://doi.org/10.1038/S41598-022-08698-9

Stampas, A., Pedroza, C., Bush, J. N., Ferguson, A. R., Kramer, J. L. K., & Hook, M. (2020). The first 24 h: opioid administration in people with spinal cord injury and neurologic recovery. Spinal Cord, 58(10), 1080–1089. https://doi.org/10.1038/s41393-020-0483-x

Teasell, R. W., Mehta, S., Aubut, J. A. L., Foulon, B., Wolfe, D. L., Hsieh, J. T. C., Townson, A. F., & Short, C. (2010). A systematic review of pharmacologic treatments of pain after spinal cord injury. Archives of Physical Medicine and Rehabilitation, 91(5), 816–831. https://doi.org/10.1016/J.APMR.2010.01.022

Terminel, M. N., Bassil, C., Rau, J., Trevino, A., Ruiz, C., Alaniz, R., & Hook, M. A. (2022). Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury. BMC Neuroscience, 23(1), 1–21. https://doi.org/10.1186/S12868-022-00739-3/FIGURES/11

Thigpen, J. C., Odle, B. L., & Harirforoosh, S. (2019). Opioids: A Review of Pharmacokinetics and Pharmacodynamics in Neonates, Infants, and Children. European Journal of Drug Metabolism and Pharmacokinetics, 44(5), 591–609. https://doi.org/10.1007/S13318-019-00552-0

Ucha, M., Coria, S. M., Núñez, A. E., Santos-Toscano, R., Roura-Martínez, D., Fernández-Ruiz, J., Higuera-Matas, A., & Ambrosio, E. (2019). Morphine self-administration alters the expression of translational machinery genes in the amygdala of male Lewis rats. Journal of Psychopharmacology, 33(7), 882–893. https://doi.org/10.1177/0269881119836206

Valkenburg, A. J., Van Den Bosch, G. E., De Graaf, J., Van Lingen, R. A., Weisglas-Kuperus, N., Van Rosmalen, J., Groot Jebbink, L. J. M., Tibboel, D., & Van Dijk, M. (2015). Long-Term Effects of Neonatal Morphine Infusion on Pain Sensitivity: Follow-Up of a Randomized Controlled Trial. The Journal of Pain, 16(9), 926–933. https://doi.org/10.1016/J.JPAIN.2015.06.007

Wang, B., Su, C. J., Liu, T. T., Zhou, Y., Feng, Y., Huang, Y., Liu, X., Wang, Z. H., Chen, L. H., Luo, W. F., & Liu, T. (2018). Neuroprotection of low-dose morphine in cellular and animal models of parkinson’s disease through ameliorating endoplasmic reticulum (ER) stress and activating autophagy. Frontiers in Molecular Neuroscience, 11, 306235. https://doi.org/10.3389/FNMOL.2018.00120/BIBTEX

Wang, X. M., Wang, X. J., & Han, J. S. (1989). Antagonistic effects of angiotensin II and morphine on synaptosomal calcium uptake. Sheng Li Xue Bao, 41(2), 179–183.

Wang, Y. L., An, X. H., Zhang, X. Q., Liu, J. H., Wang, J. W., & Yang, Z. Y. (2020). Morphine induces the apoptosis of mouse hippocampal neurons HT-22 through upregulating miR-181-5p. European Review for Medical and Pharmacological Sciences, 24(12), 7114–7121. https://doi.org/10.26355/EURREV_202006_21705

Willner, D., Cohen-Yeshurun, A., Avidan, A., Ozersky, V., Shohami, E., & Leker, R. R. (2014). Short Term Morphine Exposure In Vitro Alters Proliferation and Differentiation of Neural Progenitor Cells and Promotes Apoptosis via Mu Receptors. PLOS ONE, 9(7), e103043. https://doi.org/10.1371/JOURNAL.PONE.0103043

Woller, S. A., Moreno, G. L., Hart, N., Wellman, P. J., Grau, J. W., & Hook, M. A. (2012). Analgesia or addiction? Implications for morphine use after spinal cord injury. Journal of Neurotrauma, 29(8), 1650–1662. https://doi.org/10.1089/NEU.2011.2100

Yang, X., Wang, Y., Li, Q., Zhong, Y., Chen, L., Du, Y., He, J., Liao, L., Xiong, K., Yi, C. X., & Yan, J. (2018). The Main Molecular Mechanisms Underlying Methamphetamine- Induced Neurotoxicity and Implications for Pharmacological Treatment. Frontiers in Molecular Neuroscience, 11, 186. https://doi.org/10.3389/FNMOL.2018.00186

Young, W. (2014). Spinal cord regeneration. Cell Transplantation, 23(4–5), 573–611. https://doi.org/10.3727/096368914X678427

Zhaleh, H., Bidmeshki, P. A., & Azadbakht, M. (2020). Mesenchymal stem cell condition medium enhanced cell viability in morphine-treated cells. Bratislavske Lekarske Listy, 121(4), 263–270. https://doi.org/10.4149/BLL_2020_040

Zhang, D., Zhang, H., Jin, G. Z., Zhang, K., & Zhen, X. (2008). Single dose of morphine produced a prolonged effect on dopamine neuron activities. Molecular Pain, 4, 57. https://doi.org/10.1186/1744-8069-4-57

Zhang, H., Jia, M., Wang, X. W., Ye, C., Li, Y., Wang, N., Elefant, F., Ma, H., & Cui, C. (2019). Dentate gyrus μ-opioid receptor-mediated neurogenic processes are associated with alterations in morphine self-administration. Scientific Reports, 9(1), 1471. https://doi.org/10.1038/S41598-018-37083-8

Zhang, X. F., Liu, Z. G., Shen, W., & Gurunathan, S. (2016). Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches. International Journal of Molecular Sciences, 17(9), 1534. https://doi.org/10.3390/IJMS17091534

Zhang, Y., & Zhai, H. (2020). Bilobalide assuages morphine-induced addiction in hippocampal neuron cells through upregulation of microRNA-101. Journal of Biochemical and Molecular Toxicology, 34(7), e22493. https://doi.org/10.1002/JBT.22493

Zhao, P., Huang, Y., & Zuo, Z. (2006). Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection against ischemia in rats. Journal of Neuropathology and Experimental Neurology, 65(10), 945–952. https://doi.org/10.1097/01.JNEN.0000235123.05677.4B

Downloads

Published

2024-06-26

How to Cite

Mehrabi, A., Lashtoo Aghaee , B. and Farrokhfar, S. (2024) “The effects of morphine administration on the central nervous system (CNS): advantages and disadvantages”, Neuroscience Research Notes, 7(2), pp. 348.1–348.22. doi: 10.31117/neuroscirn.v7i2.348.