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Modulatory effect of opioid administration on the activity of cholinesterase enzyme: a systematic review of mice/rat models

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Abstract

We aimed to review the literature to find the specific effect of opioids on the activity of cholinesterase (ChE) enzyme which plays a substantial role in the functioning of cholinergic system. Literature search was performed by two independent reviewers in order to find relevant articles about the changes in the activity of ChE in mice or rat following opioid administration. Based on findings from literature review, opioid administration is able to induce cholinergic modulation via decreasing or increasing the activity of ChE enzyme. However, the degree of variation of ChE in various brain regions is different. No gender differences was reported in the effect of opioids on ChE activity. Although chronic opioid administration may decrease enzyme function, ChE activity might be unchanged following opioid withdrawal using naloxone or the development of tolerance. Opioid type affects whether or not naloxone can reverse the changes of ChE. Direct inhibitory action of morphine and the other opioid ligands believed responsible for the decrease in the ChE activity. Moreover, the potency of codeine to induce allosteric enhancement of acetylcholine receptor signaling might be involved in the cholinergic modulation of codeine and other opioids. Animal studies on rat and mice showed that opioids may change the activity of ChE. These changes can pertain an increase or decrease in enzyme activity; as there might be no change. The type of opioid used may have an effect on the cholinergic modulation. It is beneficial to conduct cross-sectional and cohort studies on addicted individuals, especially opium abusers, to find the precise association of opioids with alterations in human acetyl cholinesterase or butyrylcholinesterase. Simulation studies can also examine the structure-function relationships and provide important details to better understand the mechanism of action of opioid compounds on ChE activity. In addition, understanding how opioids impact ChE activity may help perform proper interventions for drug abstinence.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on request.

References

  • Abdel-Salam OM, Youness ER, Khadrawy YA, Sleem AA (2016) Acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis, tramadol or both. Asian Pac J Trop Med 9:1089–1094

    Article  CAS  Google Scholar 

  • Assis CR, Linhares AG, Cabrera MP, Oliveira VM, Silva KC, Marcuschi M, Carvalho EVM, Bezerra RS, Carvalho LB (2018) Erythrocyte acetylcholinesterase as biomarker of pesticide exposure: new and forgotten insights. Environ Sci Pollut Res 25:18364–18376

    Article  CAS  Google Scholar 

  • Bailey DN, Briggs JR (2005) Studies of the inhibition of serum pseudocholinesterase activity in vitro by commonly used drugs. Am J Clin Pathol 124:226–228

    Article  CAS  Google Scholar 

  • Berterame S, Erthal J, Thomas J, Fellner S, Vosse B, Clare P, Hao W, Johnson DT, Mohar A, Pavadia J (2016) Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 387:1644–1656

    Article  Google Scholar 

  • Bottoncetti A, Galli A (1987) Prevention of physostigmine-induced lethality by the opioid analgesic meptazinol in the mouse. Br J Pharmacol 91:299–306

    Article  CAS  Google Scholar 

  • Chen L, Sein M, Vo T, Amhmed S, Zhang Y, Hilaire K, Houghton M, Mao J (2014) Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia. J Opioid Manag 10:383–393

    Article  Google Scholar 

  • Dhananjayan V, Ravichandran B, Panjakumar K, Kalaiselvi K, Rajasekar K, Mala A, Avinash G, Shridhar K, Manju A, Wilson R (2019) Assessment of genotoxicity and cholinesterase activity among women workers occupationally exposed to pesticides in tea garden. Mutat Res Genet Toxicol Environ Mutagen 841:1–7

    Article  CAS  Google Scholar 

  • Draz EI, Hassan AM, Khalil HS, Elomary MA (2018) Evaluation of pelvic inflammatory disease potential in cholinesterase inhibitor pesticide-exposed females. Environ Sci Pollut Res 25:30818–30825

    Article  CAS  Google Scholar 

  • Elwy AE-HM, Tabl G (2017) Impact of tramadol and morphine abuse on the activities of acetylcholine esterase, Na+/K+-ATPase and related parameters in cerebral cortices of male adult rats. Electron Physician 9:4027–4034

    Article  Google Scholar 

  • Fisher SK, Wonnacott S (2012) Acetylcholine. In: Basic neurochemistry. Elsevier, Amsterdam

    Google Scholar 

  • Gabadadze G, Kinle A (2006) Forensic-biochemical indices of serum amilase and cholinesterase activity in lethal poisoning with heroin. Sud Med Ekspert 49:23–25

    CAS  Google Scholar 

  • Gibson A, Pollock D (1975) Reduction in the cholinesterase activity of the rat anococcygeus muscle produced by corticosterone. Br J Pharmacol 55:69–72

    Article  CAS  Google Scholar 

  • Gledhill LJ, Babey A-M (2021) Synthesis of the mechanisms of opioid tolerance: do we still say no? Cell Mol Neurobiol 41:927–948. https://doi.org/10.1007/s10571-021-01065-8

  • Hooijmans CR, Rovers MM, DE Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14:1–9

    Article  Google Scholar 

  • Howard R, Waljee J, Brummett C, Englesbe M, Lee J (2018) Reduction in opioid prescribing through evidence-based prescribing guidelines. JAMA Surg 153:285–287

    Article  Google Scholar 

  • Javed T, Habib R, Ghafoor S, Rumman B, Awan S, Ntepe LJ, Batool S, Nurulain SM (2019) Association of status of acetylcholinesterase and ACHE gene 3’UTR variants (rs17228602, rs17228616) with drug addiction vulnerability in pakistani population. Chem Biol Interact 308:130–136

    Article  CAS  Google Scholar 

  • Jitpakdee T, Mandee S (2014) Strategies for preventing side effects of systemic opioid in postoperative pediatric patients. Pediatr Anesth 24:561–568

    Article  Google Scholar 

  • Jóhannesson T (1962) Morphine as an inhibitor of brain cholinesterases in morphine-tolerant and non-tolerant rats. Acta Pharmacol Toxicol 19:23–35

    Article  Google Scholar 

  • Johnson N, Larson J, Meek E (2009) Handbook of toxicology of chemical warfare agents. Academic, San Diego

    Google Scholar 

  • Kaur G, Kaur G (2001) Role of cholinergic and GABAergic neurotransmission in the opioids-mediated GnRH release mechanism of EBP-primed OVX rats. Mol Cell Biochem 219:13–19

    Article  CAS  Google Scholar 

  • Kieffer BL (2016) Drug discovery: designing the ideal opioid. Nature 537:170–171

    Article  CAS  Google Scholar 

  • Konecka A (1992) Effect of naloxone-reversible immobilization stress on the adrenal acetylcholinesterase activity in mice. Arch Int Physiol Biochim Biophys 100:143–145

    CAS  Google Scholar 

  • Kotobuki H, Hiroshi K, Takeo K, Naohiko M (1964) Pharmacological studies of analgesics—VI: the administration of morphine and changes in acetylcholine metabolism mouse brain. Biochem Pharmacol 13:441–447

    Article  Google Scholar 

  • Mamaligas AA, Cai Y, Ford CP (2016) Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor mediated transmission. Sci Rep 6:1–11

    Article  CAS  Google Scholar 

  • Miranda H, Moreu GM, Santiago P, Wolstenholme W (1987) Castration and tolerance induces changes in the levels of the activity of acetylcholinesterase in the isolated vas deferens of the rat. Neuropharmacology 26:1529–1534

    Article  CAS  Google Scholar 

  • Mohanakumar K, Sood P (1983) Acetylcholinesterase changes in the central nervous system of mice during the development of morphine tolerance addiction and withdrawal. Brain Res Bull 10:589–596

    Article  CAS  Google Scholar 

  • Mohanakumar K, Sood P (1986) Fluctuations of acetylcholinesterase in the mouse spinal cord and in vivo sodium effect during the development of morphine tolerance, dependence, and withdrawal. Neurochem Res 11:505–520

    Article  CAS  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG, Group, P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  Google Scholar 

  • Mojtabai R (2018) National trends in long-term use of prescription opioids. Pharmacoepidemiol Drug Saf 27:526–534

    Article  Google Scholar 

  • Motel WC, Coop A, Cunningham CW (2013) Cholinergic modulation by opioid receptor ligands: potential application to Alzheimer’s disease. Mini-Rev Med Chem 13:456–466

    CAS  Google Scholar 

  • Neugebauer NM, Einstein EB, Lopez MB, Mcclure-Begley TD, Mineur YS, Picciotto MR (2013) Morphine dependence and withdrawal induced changes in cholinergic signaling. Pharmacol Biochem Behav 109:77–83

    Article  CAS  Google Scholar 

  • Oriaku E, Soliman K (1989) Effect of morphine on the rat gastrointestinal cholinergic enzymes. Arch Int Pharmacodyn Ther 297:166–177

    CAS  Google Scholar 

  • Osman NI, Baghdoyan HA, Lydic R (2005) Morphine inhibits acetylcholine release in rat prefrontal cortex when delivered systemically or by microdialysis to basal forebrain. J Am Soc Anesthesiologists 103:779–787

    CAS  Google Scholar 

  • Pade PA, Cardon KE, Hoffman RM, Geppert CM (2012) Prescription opioid abuse, chronic pain, and primary care: a co-occurring disorders clinic in the chronic disease model. J Subst Abus Treat 43:446–450

    Article  Google Scholar 

  • Pandanaboina SC, Rajbanshi S, Kunala PN, Pandanaboina S, Pandanaboina MM, Gopalreddy V, Wudayagiri R (2012) Tramadol safety-cholinergic system of rat brain without nociception. Acta Pol Pharm 69:833–841

    CAS  Google Scholar 

  • Rasool M, Malik A, Waquar S, Tul-Ain Q, Jafar TH, Rasool R, Kalsoom A, Ghafoor MA, Sehgal SA, Gauthaman K (2018) In-silico characterization and in-vivo validation of Albiziasaponin-A, Iso-Orientin, and Salvadorin using a rat model of Alzheimer’s disease. Front Pharmacol 9:730

    Article  CAS  Google Scholar 

  • Rose R, Kumar A, Bhattacharya S (1979) Striatal cholinergic activity during morphine-induced catalepsy in the rat: development of tolerance. Neurosci Lett 14:115–118

    Article  CAS  Google Scholar 

  • Schiller EY, Goyal A, Mechanic OJ (2020) Opioid overdose. StatPearls Publishing, Treasure Island

    Google Scholar 

  • Schuster D, Spetea M, Music M, Rief S, Fink M, Kirchmair J, Schütz J, Wolber G, Langer T, Stuppner H (2010) Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors. Bioorg Med Chem 18:5071–5080

    Article  CAS  Google Scholar 

  • Sivanesan E, Gitlin MC, Candiotti KA (2016) Opioid-induced hallucinations: a review of the literature, pathophysiology, diagnosis, and treatment. Anesth Analg 123:836–843

    Article  CAS  Google Scholar 

  • Türkan F (2021) Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes. Arch Physiol Biochem 127:97–101

    Article  CAS  Google Scholar 

  • Uddin MS, Rashid M (2020) Advances in neuropharmacology: drugs and therapeutics. CRC Press, Boca Raton

    Book  Google Scholar 

  • Volkow ND, Mclellan AT (2016) Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med 374:1253–1263

    Article  CAS  Google Scholar 

  • Vukšić A, Lovrić J, Konjevoda P, Blažević N, Bilušić M, Bradamante V (2019) Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats. Arh Hig Rada Toksikol 70:30–35

    Article  CAS  Google Scholar 

  • Wahba Z, Oriaku E, Soliman K (1987) Brain cholinergic involvement during the rapid development of tolerance to morphine. Pharmacology 34:66–73

    Article  CAS  Google Scholar 

  • Zhu Z, Bowman HR, Baghdoyan HA, Lydic R (2008) Morphine increases acetylcholine release in the trigeminal nuclear complex. Sleep 31:1629–1637

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran

    Hamed Aramjoo

  2. Medical Toxicology Research Center (MTRC), Mashhad University of Medical Sciences, Mashhad, Iran

    Bamdad Riahi-Zanjani

  3. Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran

    Tahereh Farkhondeh & Mahmood Sadeghi

  4. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar

  5. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar

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  1. Hamed Aramjoo
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  2. Bamdad Riahi-Zanjani
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  3. Tahereh Farkhondeh
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  4. Fatemeh Forouzanfar
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  5. Mahmood Sadeghi
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HA and MS collected the data and analyzed the full text of publications; BR-Z, TF, and FF contributed in preparation of the manuscript, and MS made the first and final drafts of the manuscript. All authors reviewed and approved the final draft.

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Correspondence to Mahmood Sadeghi.

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Aramjoo, H., Riahi-Zanjani, B., Farkhondeh, T. et al. Modulatory effect of opioid administration on the activity of cholinesterase enzyme: a systematic review of mice/rat models. Environ Sci Pollut Res 28, 52675–52688 (2021). https://doi.org/10.1007/s11356-021-16044-1

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