Advertisement

Neurochemical Research

, Volume 31, Issue 10, pp 1255–1261 | Cite as

Neurochemical Changes in Brain Induced by Chronic Morphine Treatment: NMR Studies in Thalamus and Somatosensory Cortex of Rats

  • Yun Xiang
  • Hongchang Gao
  • Hang Zhu
  • Ninglei Sun
  • Yuanye MA
  • Hao Lei
Original Paper

Abstract

To investigate the effects of chronic morphine treatment and its cessation on thalamus and the somatosensory cortex, an ex vivo high resolution (500 MHz) 1H nuclear magnetic resonance spectroscopy (NMRS), in the present study, was applied to detect multiple alterations of neurochemicals and/or neurometabolites in the rats. Ten days of chronic morphine administration was observed to markedly increase the total amount of lactate (Lac), myo-inositol (my-Ins) (each < 0.01) and aspartate (Asp) (< 0.05), and significantly decrease that of glutamate (Glu) and glutamine (Gln) in the rats thalamus (each < 0.05). In the somatosensory cortex, chronic morphine was shown to increase the level of Lac and my-Ins, and decrease that of Glu (each < 0.05). Interestingly, the ratio of Glu/GABA was found to decrease in these two brain areas after chronic morphine treatment, and among the detectable neurochemicals in those two cerebral areas, only taurine (Tau) showed to result in a significant increment in thalamus during the process of morphine discontinuation (< 0.05). Moreover, the alterations of multiple neurochemicals due to chronic morphine exhibited a tendency of recovery to the normal level over the course of morphine withdrawal. The results suggested that, in thalamus and the somatosensory cortex, chronic morphine administration and its cessation could induce multiple neurochemical changes, which may involve in the brain energy metabolism, activity and transition of neurotransmitters.

Keywords:

Morphine Withdrawal 1H magnetic resonance spectroscopy Neurochemicals Thalamus Somatosensory cortex 

Notes

Acknowledgments

This work was supported by Chinese National Science Foundation (30470553, 10234070 and 30370419) and Chinese Academy of Sciences Grants (KSCX2-SW for M.Y.).

References

  1. 1.
    Blasig J, Herz A, Reinhold K, Zieglgansberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33:19PubMedCrossRefGoogle Scholar
  2. 2.
    Espejo EF, Serrano MI, Caille S, Stinus L (2001) Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates. Neuropsychopharmacology 25:204PubMedCrossRefGoogle Scholar
  3. 3.
    Sharif NA, Hughes J (1989) Discrete mapping of brain Mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors. Peptides 10:499PubMedCrossRefGoogle Scholar
  4. 4.
    Erdos B, Lacza Z, Toth IE, Szelke E, Mersich T, Komjati K, Palkovits M, Sandor P (2003) Mechanisms of pain-induced local cerebral blood flow changes in the rat sensory cortex and thalamus. Brain Res 960:219PubMedCrossRefGoogle Scholar
  5. 5.
    Nemmani KV, Lalonde J, Mogil JS (2005) Region-specific changes of calcium/calmodulin-dependent protein kinase IV in the mouse brain following chronic morphine treatment. Neuroreport 16:879PubMedCrossRefGoogle Scholar
  6. 6.
    Diaz A, Florez J, Pazos A, Hurle MA (2000) Opioid tolerance and supersensitivity induce regional changes in the autoradiographic density of dihydropyridine-sensitive calcium channels in the rat central nervous system. Pain 86:227PubMedCrossRefGoogle Scholar
  7. 7.
    Frances H, Le Foll B, Diaz J, Smirnova M, Sokoloff P (2004) Role of DRD3 in morphine-induced conditioned place preference using drd3-knockout mice. Neuroreport 15:2245PubMedCrossRefGoogle Scholar
  8. 8.
    Sharma SK, Yashpal K, Fundytus ME, Sauriol F, Henry JL, Coderre TJ (2003) Alterations in brain metabolism induced by chronic morphine treatment: NMR studies in rat CNS. Neurochem Res 28:1369PubMedCrossRefGoogle Scholar
  9. 9.
    Seatriz JV, Hammer RP Jr (1993) Effects of opiates on neuronal development in the rat cerebral cortex. Brain Res Bull 30:523PubMedCrossRefGoogle Scholar
  10. 10.
    Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85PubMedCrossRefGoogle Scholar
  11. 11.
    Yang Y, Zheng X, Wang Y, Cao J, Dong Z, Cai J, Sui N, Xu L (2004) Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction. J Neurosci 24:2412PubMedCrossRefGoogle Scholar
  12. 12.
    Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129PubMedCrossRefGoogle Scholar
  13. 13.
    Gulya K, Gehlert DR, Wamsley JK, Mosberg H, Hruby VJ, Yamamura HI (1986) Light microscopic autoradiographic localization of delta opioid receptors in the rat brain using a highly selective bis-penicillamine cyclic enkephalin analog. J Pharmacol Exp Ther 238:720PubMedGoogle Scholar
  14. 14.
    Goodman RR, Snyder SH (1982) Kappa opiate receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects. Proc Natl Acad Sci USA 79:5703PubMedCrossRefGoogle Scholar
  15. 15.
    Lynch WC, Watt J, Krall S, Paden CM (1985) Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas. Pharmacol Biochem Behav 22:699PubMedCrossRefGoogle Scholar
  16. 16.
    Bagley EE, Gerke MB, Vaughan CW, Hack SP, Christie MJ (2005) GABA transporter currents activated by protein kinase A excite midbrain neurons during opioid withdrawal. Neuron 45:433PubMedCrossRefGoogle Scholar
  17. 17.
    O’Callaghan JP, Williams N, Clouet DH (1979) The effect of morphine on the endogenous phosphorylation of synaptic plasma membrane proteins of rat striatum. J Pharmacol Exp Ther 208:96PubMedGoogle Scholar
  18. 18.
    Cooper DM, Londos C, Gill DL, Rodbell M (1982) Opiate receptor-mediated inhibition of adenylate cyclase in rat striatal plasma membranes. J Neurochem 38:1164PubMedCrossRefGoogle Scholar
  19. 19.
    Bie B, Peng Y, Zhang Y, Pan ZZ (2005) cAMP-mediated mechanisms for pain sensitization during opioid withdrawal. J Neurosci 25:3824PubMedCrossRefGoogle Scholar
  20. 20.
    Devoto P, Flore G, Pira L, Diana M, Gessa GL (2002) Co-release of noradrenaline and dopamine in the prefrontal cortex after acute morphine and during morphine withdrawal. Psychopharmacology (Berl) 160:220CrossRefGoogle Scholar
  21. 21.
    Xu NJ, Bao L, Fan HP, Bao GB, Pu L, Lu YJ, Wu CF, Zhang X, Pei G (2003) Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J Neurosci 23:4775PubMedGoogle Scholar
  22. 22.
    Nehmad R, Nadler H, Simantov R (1982) Effects of acute and chronic morphine treatment of calmodulin activity of rat brain. Mol Pharmacol 22:389PubMedGoogle Scholar
  23. 23.
    Ding YQ, Kaneko T, Nomura S, Mizuno N (1996) Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat. J Comp Neurol 367:375PubMedCrossRefGoogle Scholar
  24. 24.
    Lewis ME, Pert A, Pert CB, Herkenham M (1983) Opiate receptor localization in rat cerebral cortex. J Comp Neurol 216:339PubMedCrossRefGoogle Scholar
  25. 25.
    Quelven I, Roussin A, Zajac JM (2004) Functional consequences of neuropeptide FF receptors stimulation in mouse: a cerebral glucose uptake study. Neuroscience 126:441PubMedCrossRefGoogle Scholar
  26. 26.
    Hao Y, Yang JY, Guo M, Wu CF, Wu MF (2005) Morphine decreases extracellular levels of glutamate in the anterior cingulate cortex: an in vivo microdialysis study in freely moving rats. Brain Res 1040:191PubMedCrossRefGoogle Scholar
  27. 27.
    Yang TT, Hung CF, Lee YJ, Su MJ, Wang SJ (2004) Morphine inhibits glutamate exocytosis from rat cerebral cortex nerve terminals (synaptosomes) by reducing Ca2+ influx. Synapse 51:83PubMedCrossRefGoogle Scholar
  28. 28.
    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 219:13PubMedCrossRefGoogle Scholar
  29. 29.
    Cruz F, Cerdan S (1999) Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed 12:451PubMedCrossRefGoogle Scholar
  30. 30.
    Haberg A, Qu H, Haraldseth O, Unsgard G, Sonnewald U (1998) In vivo injection of [1–13C]glucose and [1,2–13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 18:1223PubMedCrossRefGoogle Scholar
  31. 31.
    Vinitskaia AG, Kurbat MN, Kozlovskii AV, Lelevich VV (2005) [Chronic morphine intoxication and metabolism of neuroactive amino acids in the rat brain]. Biomed Khim 51:295PubMedGoogle Scholar
  32. 32.
    Kuriyama K, Yoneda Y (1978) Morphine induced alterations of gamma-aminobutyric acid and taurine contents and l-glutamate decarboxylase activity in rat spinal cord and thalamus: possible correlates with analgesic action of morphine. Brain Res 148:163PubMedCrossRefGoogle Scholar
  33. 33.
    Fisenko VP, Kasparov SA (1991) [The mediator spectrum of the action of morphine and the pentapeptide FK 33-824 on the neurons of the cerebral cortex]. Farmakol Toksikol 54:11PubMedGoogle Scholar
  34. 34.
    Anisimov Iu Z, Bulaev VM, Sherstnev VV (1979) [Bradykinin, morphine and naloxone interaction on the sensorimotor cortical neuron level]. Biull Eksp Biol Med 88:683PubMedGoogle Scholar
  35. 35.
    Xi ZX, Wu G, Stein EA, Li SJ (2004) Opiate tolerance by heroin self-administration: an fMRI study in rat. Magn Reson Med 52:108PubMedCrossRefGoogle Scholar
  36. 36.
    Xi ZX, Wu G, Stein EA, Li SJ (2002) GABAergic mechanisms of heroin-induced brain activation assessed with functional MRI. Magn Reson Med 48:838PubMedCrossRefGoogle Scholar
  37. 37.
    Beck T, Wenzel J, Kuschinsky K, Krieglstein J (1989) Morphine-induced alterations of local cerebral glucose utilization in the basal ganglia of rats. Brain Res 497:205PubMedCrossRefGoogle Scholar
  38. 38.
    Ross BD (1991) Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; myo-inositol and related metabolites. NMR Biomed 4:59Google Scholar
  39. 39.
    Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289PubMedGoogle Scholar
  40. 40.
    Nadler JV, Cooper JR (1972) N-acetyl-l-aspartic acid content of human neural tumours and bovine peripheral nervous tissues. J Neurochem 19:313PubMedCrossRefGoogle Scholar
  41. 41.
    Hardy DL, Norwood TJ (1998) Spectral editing technique for the in vitro and in vivo detection of taurine. J Magn Reson 133:70PubMedCrossRefGoogle Scholar
  42. 42.
    Vinnitskaia AG, Kurbat MN, Lelevich VV, Kozlovskii AV (2005) [GABA metabolism and contents of neuroactive amino acids in rat brain after acute morphine administration]. Biomed Khim 51:81PubMedGoogle Scholar
  43. 43.
    Kurbat MN, Lelevich VV (2002) [Metabolism of neuroactive amino acids in the rat cerebral cortex during morphine intoxication]. Eksp Klin Farmakol 65:27PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Yun Xiang
    • 1
    • 3
    • 4
  • Hongchang Gao
    • 1
    • 3
  • Hang Zhu
    • 1
    • 3
  • Ninglei Sun
    • 2
    • 3
  • Yuanye MA
    • 2
  • Hao Lei
    • 1
  1. 1.State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and MathematicsThe Chinese Academy of SciencesWuhanPeoples Republic of China
  2. 2.Section of Cognitive Brain Research, Kunming Institute of ZoologyThe Chinese Academy of SciencesKunmingPeoples Republic of China
  3. 3.Graduate School of the Chinese Academy of SciencesBeijingPeoples Republic of China
  4. 4.School of Medicine & Life ScienceJianghan UniversityWuhanPeoples Republic of China

Personalised recommendations