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Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia of propofol in mice

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Abstract

The effects of intracerebroventricular (icv) agonists and antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the general anesthesia of propofol were studied. A total of 144 Kunming mice, male and female with body mass of (22±3) g, were used. Part One of the Experiment: a total of 104 Kunming mice, male and female, were randomly divided into 13 groups. Intracerebroventricular artificial cerebral fluid (aCSF) or different doses of NMDA, AMPA, MK-801 or NBQX was injected immediately after intravenously administered propofol 25 mg/kg and the recovery time following the loss of righting reflex (LORR) was recorded. Part Two of the Experiment: a total of 40 Kunming female mice were divided randomly into 5 groups and injected with icv aCSF or NMDA, AMPA, MK-801 or NBQX after intraperitoneally administered propofol 50 mg/kg. The pain threshold of the mice was then investigated by hot-plate test (HPPT). NMDA (0.05 or 0.075μg, icv) or AMPA (0.05 μg, icv) exhibited no effects on the LORR, but NMDA (0.1 μg, icv) or AMPA (0.075 or 0.1 μg, icv) prolonged the LORR significantly compared with the aCSF group (P<0.05, P<0.01). The LORR of the 2 μg MK-801 group had no changes, while those of the 4 or 8 μg MK-801 groups were prolonged significantly. The LORR of the 0.5, 2 or 4 μg NBQX groups were all prolonged significantly. NMDA 0.05 μg or AMPA 0.05 μg decreased the pain threshold slightly but did not differ in effect compared with the aCSF group; 2 μg MK-801 or 0.5 μg NBQX both increased the pain threshold significantly. Our results indicate that propofol produces general anesthesia partly through an interaction with brain NMDA and AMPA receptors in mice.

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References

  1. Sawada S, Yamamoto C. Blocking action of pentobarbital on receptors for excitatory amino acids in the guinea pig hippocampus. Exp Brain Res, 1985, 59(2): 226–231

    Article  CAS  PubMed  Google Scholar 

  2. Twombly D A, Herman M D, Kye C H, Narahashi T. Ethanol effects on two types of voltage activated calcium channels. J Pharmacol Exp Ther, 1990, 254(3): 1029–1037

    CAS  PubMed  Google Scholar 

  3. Bertlik M, Orser B A, Wang L Y, MacDonald J F. Propofol selectively inhibits the NMDA subtye of glutamate receptor. Can J Anesth, 1994, 41: A6

    Article  Google Scholar 

  4. Zhu H, Cottrell J E, Kass I S. The effect of thiopental and propofol on NMDA-and AMPA-mediated glutamate excitotoxicity. Anesthesiology, 1997, 87(4): 944–951

    Article  CAS  PubMed  Google Scholar 

  5. Orser B A, Bertlik M, Wang L Y, MacDonald J F. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurons. Br J Pharmacol, 1995, 116(2): 1761–1768

    Article  CAS  PubMed  Google Scholar 

  6. Xu A J, Duan S M, Zeng Y M. Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on antinociception of propofol. Acta Pharmacol Sin, 2004, 25(1): 9–14

    PubMed  Google Scholar 

  7. Bansinath M, Shukla V K, Turndorf H. Popofol modulates the effects of chemoconvulsants acting at GABAergic, glycinergic, and glutamate receptor subtypes. Anesthesiology, 1995, 83(4): 809–815

    Article  CAS  PubMed  Google Scholar 

  8. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983, 16(1): 109–110

    Article  CAS  PubMed  Google Scholar 

  9. Xu S Y, Bian R L, Chen X, ed. Methodology of Pharmacological Experiments. 3rd ed. Beijing: People’s Medical Publishing House, 2002, 184: 886–887

    Google Scholar 

  10. Zhang C Y, Zhu T J, Hu G X, Chen X Y, Liu D X, Chen Z K. Effect of sodium dimercaptopropanesulfonate on antagonism of tetramethyl enedisulphotetra mine to GABA receptor. Acta Pharmacol Sin, 2001, 22(5): 435–439

    PubMed  Google Scholar 

  11. Irifune M, Takarada T, Shimizu Y, Endo C, Katayama S, Dohi T, Kawahara M. Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors. Anesth Analg, 2003, 97(2): 424–429

    Article  CAS  PubMed  Google Scholar 

  12. Anwar M M, Abdel-Rahman M S. Effect of propofol on perception of pain in mice: mechanism of action. Comp Biochem Physiol A Mol Integr Physiol, 1998, 120(2): 249–253

    Article  CAS  PubMed  Google Scholar 

  13. Hudspith M J. Glutamate: A role in normal brain function, anesthesia, analgesia and CNS injury. Br J Anaesth, 1997, 78(6): 731–747

    Article  CAS  PubMed  Google Scholar 

  14. Kitamura A, Marszalec W, Yeh J Z, Narahashi T. Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons. J Pharmacol Exp Ther, 2003, 304(1): 162–171

    Article  CAS  PubMed  Google Scholar 

  15. Wakasugi M, Hirota K, Roth S H, Ito Y. The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. Anesth Analg, 1999, 88(3): 676–680

    CAS  PubMed  Google Scholar 

  16. Grasshoff C, Gillessen T. The effect of propofol on increased superoxide concentration in cultured rat cerebrocortical neurons after stimulation of N-methyl-d-aspartate receptors. Anesth Analg, 2002, 95(4): 920–922

    CAS  PubMed  Google Scholar 

  17. Aanonsen L M, Wilcox G L. Nociceptive action of excitatory amino acids in the mouse: Effects of spinally administered opioids, phencyclidine and sigma agonists. J Pharmacol Exp Ther, 1987, 243(1): 9–19

    CAS  PubMed  Google Scholar 

  18. Lutfy K, Cai S X, Woodward R M, Weber E. Antinociceptive effects of NMDA and non-NMDA receptor antagonists in the tail flick test in mice. Pain, 1997, 70(1): 31–40

    Article  CAS  PubMed  Google Scholar 

  19. Yamakura T, Sakimura K, Shimoji K, Mishina M. Effects of propofol on various AMPA-, kainate-and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci Lett, 1995, 188(3): 187–190

    Article  CAS  PubMed  Google Scholar 

  20. Miller R D. Anesthesia. 5th ed. Harcourt Asia: Churchill Livingstone, 2001, 249–256

    Google Scholar 

  21. Buggy D J, Nicol B, Rowbotham D J, Lambert D G. Effects of intravenous anesthetic agents on glutamate release: A role for GABAA receptor-mediated inhibition. Anesthesiology, 2000, 92(4): 1067–1073

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Tian Yuke MD.

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Xu, A., Duan, S. & Tian, Y. Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia of propofol in mice. Front. Med. China 1, 207–210 (2007). https://doi.org/10.1007/s11684-007-0039-x

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  • DOI: https://doi.org/10.1007/s11684-007-0039-x

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