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Hyperbaric Oxygen Attenuates Withdrawal Symptoms by Regulating Monoaminergic Neurotransmitters and NO Signaling Pathway at Nucleus Accumbens in Morphine-Dependent Rats

Abstract

In this study, we examined whether hyperbaric oxygen (HBO2) plays a detoxification role in withdrawal symptoms in a morphine-dependent rat model. The model was established through injections of morphine at increasing doses for 7 days. Withdrawal symptoms were induced by naloxone injection on the 8th day. The detoxification effect of HBO2 was evaluated using the withdrawal symptom scores, biochemical indices and neurotransmitters. Compared with the model group, HBO2 therapy significantly attenuated the withdrawal symptom scores, body weight loss and the level of norepinephrine level, whereas it increased the dopamine level and tyrosine hydroxylase expression in the nucleus accumbens. Moreover, HBO2 therapy substantially alleviated the NO, NOS, cAMP, and cGMP levels. Our findings indicate that HBO2 can effectively alleviate withdrawal symptoms induced by morphine dependence, and these effects may be attributed to the modulation of monoaminergic neurotransmitters and the suppression of the NO–cGMP signaling pathway.

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References

  1. UNDOC (2016) World Drug Report 2016. New York: United Nations. http://www.unodc.org/wdr2016/

  2. Maldonado R, Koob GF (1993) Destruction of the locus coeruleus decreases physical signs of opiate withdrawal. Brain Res 605:128–138

    CAS  PubMed  Google Scholar 

  3. Joseph H, Stancliff S, Langrod J (2000) Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med 67:347–364

    CAS  PubMed  Google Scholar 

  4. Georges F, Aston-Jones G (2003) Prolonged activation of mesolimbic dopaminergic neurons by morphine withdrawal following clonidine: participation of imidazoline and norepinephrine receptors. Neuropsychopharmacology 28:1140–1149

    CAS  PubMed  Google Scholar 

  5. Wise RA (1989) Opiate reward: sites and substrates. Neurosci Biobehav Rev 13:129–133

    CAS  PubMed  Google Scholar 

  6. Di Chiara G, Bassareo V (2007) Reward system and addiction: what dopamine does and doesn’t do. Curr Opin Pharmacol 7:69–76

    PubMed  Google Scholar 

  7. Wu G, Huang W, Zhang H, Li Q, Zhou J, Shu H (2011) Inhibitory effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats. J Ethnopharmacol 136:254–259

    PubMed  Google Scholar 

  8. Wan C, Zhihuan N, Yaoxuan L, Jianping H, Chunxia C, Luying H (2017) Role of dopamine signaling in drug addiction. Curr Top Med Chem 17:2440–2455

    Google Scholar 

  9. Ventura R, Alcaro A, Puglisi-Allegra S (2005) Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbens. Cereb Cortex 15:1877–1886

    PubMed  Google Scholar 

  10. Dambisya YM, Lee TL (1996) Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice. Br J Pharmacol 117:914–918

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lue WM, Su MT, Lin WB, Tao PL (1999) The role of nitric oxide in the development of morphine tolerance in rat hippocampal slices. Eur J Pharmacol 383:129–135

    CAS  PubMed  Google Scholar 

  12. Murad F (2004) Discovery of some of the biological effects of nitric oxide and its role in cell signaling. Biosci Rep 24:452–474

    PubMed  Google Scholar 

  13. Shen F, Li YJ, Shou XJ, Cui CL (2012) Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory. Neurobiol Learn Mem 98:130–138

    CAS  PubMed  Google Scholar 

  14. Zhu XZ, Luo LG (1992) Effect of nitroprusside (nitric oxide) on endogenous dopamine release from rat striatal slices. J Neurochem 59:932–935

    CAS  PubMed  Google Scholar 

  15. Calignano A, Persico P, Mancuso F, Sorrentino L (1993) Endogenous nitric oxide modulates morphine-induced changes in locomotion and food intake in mice. Eur J Pharmacol 231:415–419

    CAS  PubMed  Google Scholar 

  16. Dekleva M, Neskovic A, Vlahovic A, Putnikovic B, Beleslin B, Ostojic M (2004) Adjunctive effect of hyperbaric oxygen treatment after thrombolysis on left ventricular function in patients with acute myocardial infarction. Am Heart J 148:589

    CAS  Google Scholar 

  17. Bennett MH, Lehm JP, Jepson N (2015) Hyperbaric oxygen therapy for acute coronary syndrome. Cochrane Database Syst Rev 23:CD004818

    Google Scholar 

  18. Stetler RA, Leak RK, Gan Y, Li P, Zhang F, Hu X, Jing Z, Chen J, Zigmond MJ, Gao Y (2014) Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance. Prog Neurobiol 114:58–83

    PubMed  Google Scholar 

  19. Chen C, Chen W, Nong Z, Ma Y, Qiu S, Wu G (2016) Cardioprotective effects of combined therapy with hyperbaric oxygen and diltiazem pretreatment on myocardial ischemia-reperfusion injury in rats. Cell Physiol Biochem 38:2015–2029

    CAS  PubMed  Google Scholar 

  20. Pan X, Chen C, Huang J, Wei H, Fan Q (2015) Neuroprotective effect of combined therapy with hyperbaric oxygen and madopar on 6-hydroxydopamine-induced Parkinson’s disease in rats. Neurosci Lett 600:220–225

    CAS  PubMed  Google Scholar 

  21. Chen X, Li Y, Chen W, Nong Z, Huang J, Chen C (2016) Protective effect of hyperbaric oxygen on cognitive impairment induced by D-galactose in mice. Neurochem Res 41:3032–3041

    CAS  PubMed  Google Scholar 

  22. Chen C, Huang L, Nong Z, Li Y, Chen W, Huang J, Pan X, Wu G, Lin Y (2017) Hyperbaric oxygen prevents cognitive impairments in mice induced by D-galactose by improving cholinergic and anti-apoptotic functions. Neurochem Res 42:1240–1253

    CAS  PubMed  Google Scholar 

  23. Nicoara D, Zhang Y, Nelson JT, Brewer AL, Maharaj P, DeWald SN, Shirachi DY, Quock RM (2016) Hyperbaric oxygen treatment suppresses withdrawal signs in morphine-dependent mice. Brain Res 1:434–437

    Google Scholar 

  24. Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ (1990) Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 10:2308–2317

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen C, Nong Z, Huang J, Chen Z, Zhang S, Jiao Y, Chen X, Huang R (2014) Yulangsan polysaccharide attenuates withdrawal symptoms and regulates the NO pathway in morphine-dependent rats. Neurosci Lett 570:63–68

    CAS  PubMed  Google Scholar 

  26. Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic Press, London

    Google Scholar 

  27. Chen C, Lu W, Wu G, Lv L, Chen W, Huang L, Wu X, Xu N, Wu Y (2017) Cardioprotective effects of combined therapy with diltiazem and superoxide dismutase on myocardial ischemia-reperfusion injury in rats. Life Sci 183:50–59

    CAS  PubMed  Google Scholar 

  28. Koob GF, Stinus L, Le Moal M, Bloom FE (1989) Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence. Neurosci Biobehav Rev 13:135–140

    CAS  PubMed  Google Scholar 

  29. San-Martin-Clark O, Cuellar B, Leza JC, Lizasoain I, Lorenzo P (1996) Effects of trepelennamine on brain monoamine turnover in morphine dependent and abstinent mice. Psychopharmacology 123:297–302

    CAS  PubMed  Google Scholar 

  30. Maruyama Y, Takemori AE (1973) The role of dopamine and norepinephrine in the naloxone-induced abstinence of morphine-dependent mice. J Pharmacol Exp Ther 185:602–608

    CAS  PubMed  Google Scholar 

  31. Huggins AK, Nelson DR (1975) The effect of hyperbaric oxygenation on the levels of 5-hydroxytryptamine, noradrenaline, dopamine and free amino acids in whole mouse brain. J Neurochem 25:117–121

    CAS  PubMed  Google Scholar 

  32. Lavoute C, Weiss M, Risso JJ, Rostain JC (2017) Examination of the role of NMDA and GABAA receptors in the effects of hyperbaric oxygen on striatal dopamine levels in rats. Neurochem Res 42:1116–1122

    CAS  PubMed  Google Scholar 

  33. Lavoute C, Weiss M, Risso JJ, Rostain JC (2014) Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats. Neurochem Res 39:287–294

    CAS  PubMed  Google Scholar 

  34. Yang ZJ, Camporesi C, Yang X, Wang J, Bosco G, Lok J, Gorji R, Schelper RL, Camporesi EM (2002) Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion. Eur J Appl Physiol 87:101–107

    CAS  PubMed  Google Scholar 

  35. Faiman MD, Hable A, Mehl RG (1969) Hyperbaric oxygenation and brain norepinephrine and 5-hydroxytryptamine: oxygen-pressure interactions. Life Sci 8:1163–1178

    CAS  PubMed  Google Scholar 

  36. Maruyama Y, Hayashi G, Smits SE, Takemori AE (1971) Studies on the relationship between 5-hydroxytryptamine turnover in brain and tolerance and physical dependence in mice. J Pharmacol Exp Ther 178:20–29

    CAS  PubMed  Google Scholar 

  37. Bredt DS, Snyder SH (1992) Nitric oxide, a novel neuronal messenger. Neuron 8:3–11

    CAS  PubMed  Google Scholar 

  38. Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67

    CAS  PubMed  Google Scholar 

  39. Knowles RG, Moncada S (1992) Nitric oxide as a signal in blood vessels. Trends Biochem Sci 17:399–402

    CAS  PubMed  Google Scholar 

  40. Elayan IM, Axley MJ, Prasad PV, Ahlers ST, Auker CR (2000) Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain. J Neurophysiol 83:2022–2029

    CAS  PubMed  Google Scholar 

  41. Ohgami Y, Chung E, Shirachi DY, Quock RM (2008) The effect of hyperbaric oxygen on regional brain and spinal cord levels of nitric oxide metabolites in rat. Brain Res Bull 75:668–673

    CAS  PubMed  Google Scholar 

  42. Uusijarvi J, Eriksson K, Larsson AC, Nihlen C, Schiffer T, Lindholm P, Weitzberg E (2015) Effects of hyperbaric oxygen on nitric oxide generation in humans. Nitric Oxide 44:88–97

    PubMed  Google Scholar 

  43. Han G, Li L, Meng LX (2013) Effects of hyperbaric oxygen on pain-related behaviors and nitric oxide synthase in a rat model of neuropathic pain. Pain Res Manag 18:137–141

    PubMed  PubMed Central  Google Scholar 

  44. Ding Y, Yao P, Hong T, Han Z, Zhao B, Chen W (2017) The NO-cGMP-PKG signal transduction pathway is involved in the analgesic effect of early hyperbaric oxygen treatment of neuropathic pain. J Headache Pain 18:51

    PubMed  PubMed Central  Google Scholar 

  45. Zhang J, Sam AD, Klitzman B, Piantadosi CA (1995) Inhibition of nitric oxide synthase on brain oxygenation in anesthetized rats exposed to hyperbaric oxygen. Undersea Hyperb Med 22:377–382

    CAS  PubMed  Google Scholar 

  46. Pulvirenti L, Balducci C, Koob GF (1996) Inhibition of nitric oxide synthesis reduces intravenous cocaine self-administration in the rat. Neuropharmacology 35:1811–1814

    CAS  PubMed  Google Scholar 

  47. Gholami A, Haeri-Rohani A, Sahraie H, Zarrindast MR (2002) Nitric oxide mediation of morphine-induced place preference in the nucleus accumbens of rat. Eur J Pharmacol 449:269–277

    CAS  PubMed  Google Scholar 

  48. Pulvirenti L, Berrier R, Kreifeldt M, Koob GF (1994) Modulation of locomotor activity by NMDA receptors in the nucleus accumbens core and shell regions of the rat. Brain Res 664:231–236

    CAS  PubMed  Google Scholar 

  49. Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278:58–63

    CAS  PubMed  Google Scholar 

  50. Yu VC, Eiger S, Duan DS, Lameh J, Sadee W (1990) Regulation of cyclic AMP by the mu-opioid receptor in human neuroblastoma SH-SY5Y cells. J Neurochem 55:1390–1396

    CAS  PubMed  Google Scholar 

  51. Punch LJ, Self DW, Nestler EJ, Taylor JR (1997) Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray. J Neurosci 17:8520–8527

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81701089), the Guangxi Natural Science Foundation (2017GXNSFBA198010, 0728081 and 0832209), the Guangxi Sanitation Research Project (Z20170380, Z20170329, Z2016582, Z2016189, Z2012283, Z2012312, Z2013342 and GZPT1243) and the Independent Research and Development Project of Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards (201606).

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Correspondence to Xiaorong Pan or Shengyong Lan.

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Chen, C., Fan, Q., Nong, Z. et al. Hyperbaric Oxygen Attenuates Withdrawal Symptoms by Regulating Monoaminergic Neurotransmitters and NO Signaling Pathway at Nucleus Accumbens in Morphine-Dependent Rats. Neurochem Res 43, 531–539 (2018). https://doi.org/10.1007/s11064-017-2447-x

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  • DOI: https://doi.org/10.1007/s11064-017-2447-x

Keywords

  • Hyperbaric oxygen
  • Withdrawal symptoms
  • Morphine dependence
  • Neurotransmitters
  • NO–cGMP signaling pathway