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Morphine Withdrawal as a State of Glutamate Hyperactivity

The Effects of Glutamate Receptor Subtype Ligands on Morphine-Withdrawal Symptoms

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Book cover Glutamate and Addiction

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Cessation of the repeated administration of opiates results in a characteristic morbidity in humans, including anxiety, nausea, insomnia, hot and cold flashes, muscle aches, perspiration, and diarrhea (1). Great strides have been made in understanding the neurophysiology underlying these opiate-withdrawal symptoms. Several neurotransmitter systems have been shown to play an important role in opiate withdrawal, including the dopaminergic (2–4) and cholinergic (5–7) systems. This chapter will discuss evidence for a role of the glutamate system in morphine withdrawal. Specifically, the idea that morphine withdrawal is a state of glutamate hyperactivity in defined brain regions will be discussed. One of those brain regions is the locus coeruleus.

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References

  1. Kolb, L. and Hinunelsbach, C. K. (1938) Clinical studies of drug addiction, III. A critical review of the withdrawal treatments with method of evaluating abstinence syndromes. Am. J. Psychiatry 94, 759–764.

    Google Scholar 

  2. Pathos, E., Rada, P., Mark, G. P., and Hoebel, B. G. (1991) Dopamine microdialysis in the nucleus accumbens during acute and chronic, naloxone-precipitated withdrawal and clonidine treatment. Brain Res. 566, 348–350.

    Google Scholar 

  3. Harris, G. C. and Aston-Jones, G. A. (1994) Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature 371, 155–157.

    PubMed  CAS  Google Scholar 

  4. Druhan, J. P., Walters, C. L., and Aston-Jones, G. (2000) Behavioral activation induced by D2-like receptor stimulation during opiate withdrawal. J. Pharmcol. Exp. Thee. 294, 531–538.

    CAS  Google Scholar 

  5. Buccafusco, J. J. (1991) Inhibition of the morphine withdrawal syndrome by a novel muscarinic antagonist (4-DAMP). Life Sci. 48, 749–756.

    PubMed  CAS  Google Scholar 

  6. Buccafusco, J. J. (1992) Neuropharmacologic and behavioral actions of clonidine: interactions with central neurotransmitters. Int. Rev. Neurobiol. 33, 55–107.

    PubMed  CAS  Google Scholar 

  7. Zhang, L. C. and Buccafusco, J. J. (2000) Adaptive changes in M1 muscarinic receptors localized to specific rostral brain regions during and after morphine withdrawal. Neuropharmacology 39, 1720–1734.

    PubMed  CAS  Google Scholar 

  8. Dahlstrom, A. and Fuxe, K. (1965) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neurons. Acta Physiol. Scand. 232 (Suppl.), 1–55.

    Google Scholar 

  9. Foote, S. L., Bloom, F. E., and Aston-Jones, G. (1983) Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiol. Rev. 63, 844–914.

    PubMed  CAS  Google Scholar 

  10. Jones, B. E. and Moore, R. Y. (1977) Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study. Brain Res. 127, 23–53.

    Google Scholar 

  11. Nygren, L. G. and Olson, L. (1977) A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord. Brain Res. 132, 85–93.

    PubMed  CAS  Google Scholar 

  12. Cedarbaum, J. M. and Aghajanian, G. K. (1978) Activation of locus coeruleus neurons by peripheral stimuli: modulation by a collateral inhibitory mechanism. Life Sci. 23, 1383–1392.

    PubMed  CAS  Google Scholar 

  13. Aston-Jones, G., Ennis, M., Pieribone, V. A., Nickell, W. T., and Shipley, M. T. (1986) The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 234, 734–737.

    PubMed  CAS  Google Scholar 

  14. Luppi, P. H., Aston-Jones, G., Akaoka, H., Chouvet, G., and Jouvet, M. (1995) Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and phaseolus vulgaris leucoagglutinin. Neuroscience 65, 119–160.

    PubMed  CAS  Google Scholar 

  15. Valentino, R. J., Curtis, A. L., Page, M. E., Pavcovich, L. A., and Florin-Lechner, S. M. (1998) Activation of the locus coeruleus brain noradrenergic system during stress: circuitry, consequences, and regulation. Adv. Pharmacol. 42, 781–784.

    PubMed  CAS  Google Scholar 

  16. Van Bockstaele, E. J., Bajic, D., Proudfit, H., and Valentino, R. J. (2001) Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus. Physiol. Behay. 73, 273–283.

    Google Scholar 

  17. Ennis, M. and Aston-Jones, G. (1988) Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain. J. Neurosci. 8, 3644–3657.

    PubMed  CAS  Google Scholar 

  18. Rasmussen, K. and Aghajanian, G. K. (1989) Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis. Brain Res. 505, 346–350.

    PubMed  CAS  Google Scholar 

  19. Aghajanian, G. K. (1978) Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature 276, 186–187.

    PubMed  CAS  Google Scholar 

  20. Valentino, R. J. and Wehby, R. G. (1989) Locus coeruleus discharge characteristics of morphine-dependent rats: Effects of naltrexone. Brain Res. 488, 126–134.

    PubMed  CAS  Google Scholar 

  21. Rasmussen, K., Beitner, D. B., Krystal, J. H., Aghajanian, G. K., and Nestler, E. J. (1990) Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological and biochemical correlates. J. Neurosci. 10, 2308–2317.

    PubMed  CAS  Google Scholar 

  22. Akaoka, H. and Aston-Jones, G. A. (1991) Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input. J. Neurosci. 11, 3830–3839.

    PubMed  CAS  Google Scholar 

  23. Crawley, J. N., Laverty, R., and Roth, R. (1979) Clonidine reversal of increased norepinephrine metabolite levels during morphine withdrawal. Eur. J. Pharm. 57, 247–250.

    CAS  Google Scholar 

  24. Laverty, R. and Roth, R. H. (1980) Clonidine reverses the increased norepinephrine turnover during morphine withdrawal in rats. Brain Res. 182, 482.

    PubMed  CAS  Google Scholar 

  25. Done, C., Silverstone, P., and Sharp, T. (1992) Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in rat hippocampus in vivo. Eur. J. Pharm. 215, 333–336.

    CAS  Google Scholar 

  26. Tseng, L. F., Loh, H. H., and Wei, E. T. (1975) Effects of clonidine on morphine withdrawal signs in the rat. Eur. J. Pharmacol. 30, 93–99.

    PubMed  CAS  Google Scholar 

  27. Gold, M. S., Redmond, D. E., Jr., and Kleber, H. D. (1978) Clonidine blocks acute opiate-withdrawal symptoms. Lancet 2, 599–602.

    PubMed  CAS  Google Scholar 

  28. Taylor, J. R., Elsworth, J. D., Garcia, E. J., Grant, S. J., Roth, R. H., and Redmond, D. E., Jr. (1988) Clonidine infusion into the locus coeruleus attenuates behavioral and neurochemical changes associated with naloxone-precipitated withdrawal. Psychopharmacology 96, 121–134.

    PubMed  CAS  Google Scholar 

  29. Maldonado, R. and Koob, G. F. (1993) Destruction of the locus coeruleus decreases physical signs of opiate withdrawal. Brain Res. 605, 128–138.

    PubMed  CAS  Google Scholar 

  30. Maldonado, R., Stinus, L., Gold, L. H., and Koob, G. F., (1992) Role of different brain structures in the expression of the physical morphine withdrawal syndrome. J. Pharmacol. Exp. Ther. 261, 669–677.

    PubMed  CAS  Google Scholar 

  31. Caille, S., Espejo, E. F., Reneric, J., Cador, M., Koob, G. F., and Stinus, L. (1999) Total neurochemical lesion of noradrenergic neurons of the locus coeruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal. J. Pharmacol. Exp. Thee 290, 881–892.

    CAS  Google Scholar 

  32. Delfs, J. M., Zhu, Y., Druhan, J. P., and Aston-Jones, G. (2000) Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403, 430–434.

    PubMed  CAS  Google Scholar 

  33. MacDonald, J. C., Williams, J. T., Osborne, P. B., and Bellchambers, C. E. (1997) Where is the locus in opioid withdrawal? TIPS 18, 134–140.

    Google Scholar 

  34. Conn, P. J. and Pin, J. P. (1997) Pharmacology and functions of metabotropic glutamate receptors. Anon. Rev. Pharmacol. 37, 205–237.

    CAS  Google Scholar 

  35. Schoepp, D. D. and Conn, J. P. (1993) Metabotropic glutamate receptors in brain function and pathology. Trends Pharm. Sci. 14, 13–20.

    PubMed  CAS  Google Scholar 

  36. Pin, J. P. and Duvoisin, R. (1994) The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34, 1–26.

    Google Scholar 

  37. Herrero, I., Miras-Portugal, M. T., and Sanches-Prieto, J. (1992) Positive feedback of glutamate exocytoses by metabotropic presynaptic receptor stimulation. Nature 360, 163–166.

    PubMed  CAS  Google Scholar 

  38. Gereau, R. W. and Conn, P. J. (1995) Multiple presynaptic metabotropic glutamate receptors modulate excitatory and inhibitory synaptic transmission in hippocampal area CA1. J. Neurosci. 15, 6879–6889.

    PubMed  CAS  Google Scholar 

  39. Cartmell, J. and Schoepp, D. D. (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neurochem. 75, 889–907.

    PubMed  CAS  Google Scholar 

  40. Rasmussen, K., Krystal, J. H., and Aghajanian, G. K. (1991) Excitatory amino acids and morphine withdrawal: diffferential effects of central and peripheral kynurenic acid administration. Psychopharmacology 105, 508–512.

    PubMed  CAS  Google Scholar 

  41. Tung, C. S., Grenhoff, J., Svensson, T. H. (1990) Morphine withdrawal responses of rat locus coeruleus neurons are blocked by an excitatory amino-acid antagonist. Acta Phys. Scand. 138, 581–582.

    CAS  Google Scholar 

  42. Aghajanian, G. K., Kogan, J. H., and Moghaddam, B. (1994) Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: an in vivo microdialysis study. Brain Res. 636, 126–130.

    PubMed  CAS  Google Scholar 

  43. Zhang, T., Feng, Y., Rockhold, R. W., and Ho, I. K. (1994) Naloxone-precipitated morphine withdrawal increases pontine glutamate levels in the rat. Life Sci. 55, PL25–PL31.

    Google Scholar 

  44. Feng, Y. Z., Zhang, T., Rockhold, R. W., and Ho I. K. (1995) Increased locus coeruleus glutamate levels are associated with naloxone-precipitated withdrawal from butorphanol in the rat. Neurochem. Res. 20, 745–751.

    PubMed  CAS  Google Scholar 

  45. Hoshi, K., Ma, T, and Ho, I. K. (1996) Precipitated x-opioid receptor agonist withdrawal increases glutamate in rat locus coeruleus. Eur. J. Pharmacol. 314, 301–30.

    PubMed  CAS  Google Scholar 

  46. Koob, G. F. and Bloom, F. E., (1988) Cellular and molecular mechanisms of drug dependence. Science 242, 715–723.

    PubMed  CAS  Google Scholar 

  47. Koob, G. F., Wall, T. L., and Bloom F. E. (1989) Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal. Psychopharmacology 98, 530–534.

    PubMed  CAS  Google Scholar 

  48. Stinus, L., Le Moal, M., and Koob, G. F. (1990) Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37, 767–773.

    PubMed  CAS  Google Scholar 

  49. Walters, C. L., Aston-Jones, G., and Druhan, J. P. (2000) Expression of Fos-related antigens in the nucleus accumbens during opiate withdrawal and their attenuation by a D2 dopamine receptor agonist. Neuropsychopharmacology 23, 307–315.

    PubMed  CAS  Google Scholar 

  50. Harris, G. and Aston-Jones, G. (2001) Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal. Neuropsychopharmacology 22, 75–85.

    Google Scholar 

  51. Sepulveda, M. J., Hernandez, L., Rada, E, Tucci, S., and Contreras, E. (1998) Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: an in vivo microdialysis study. Pharmacol. Biochem. Behay. 60, 255–262.

    CAS  Google Scholar 

  52. Jhamandas, K. H., Marsala, M., Ibuki, T., and Yaksh, T. L. (1996) Spinal amino acid release and precipitated withdrawal in rats chronically infused with spinal morphine. J. Neurosci. 16, 2758–2766.

    PubMed  CAS  Google Scholar 

  53. Ozawa, T., Nakagawa, T., Shige, K., Minami, M., and Satoh, M. (2001) Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal. Brain Res. 905, 245–258.

    Google Scholar 

  54. Manzoni, O. J. and Williams, J. T. (1999) Presynaptic regulation of glutamate release in the ventral tegmental area during morphine withdrawal../. Neurosci. 19, 6629–6636.

    CAS  Google Scholar 

  55. Herman, B. H., Vocci, F., and Bridge, P. (1995) The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal: medication development issues for opiate addiction. Neuropsychopharmacology 13, 269–294.

    PubMed  CAS  Google Scholar 

  56. Herman, B. H. and O’Brien, C. P. (1997) Clinical medications development for opiate addiction: focus on nonopioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention. Sem. Neuroscience 9, 158–172.

    CAS  Google Scholar 

  57. Trujillo, K. A. and Akil, H. (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251, 85–87.

    PubMed  CAS  Google Scholar 

  58. Tiseo, P. J. and Inturrisi, C. E. (1993) Attenuation and reversal of morphine tolerance by the competitive N-Methyl-DAspartate receptor antagonist, LY274614. J. Pharmacol. Exp. Ther. 264, 1090–1096.

    PubMed  CAS  Google Scholar 

  59. Tiseo, P. J., Cheng, J., Pasternak, G. W., and Inturrisi, C. E. (1994) Modulation of morphine tolerance by the competitive Nmethyl-n-aspartate receptor antagonist LY274614: assesment of opioid receptor changes. J. Pharmacol. Exp. Ther. 268, 195–201.

    PubMed  CAS  Google Scholar 

  60. Elliott, K., Minami, N., Kolesnikov, Y. A., Pasternak, G. W., and Inturrisi, C. E. (1994) The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the muopioid morphine but not to kappa opioids. Pain 56, 69–74.

    PubMed  CAS  Google Scholar 

  61. Rasmussen, K, Fuller, R. W., Stockton, M. E., Perry, K. W., Swinford, R. M., and Ornstein, P. L. (1991b) NMDA receptor antagonists suppress behaviors but not norepinephrine turnover or locus coeruleus unit activity induced by opiate withdrawal. Eur. J. Pharmacol. 117, 9–16.

    Google Scholar 

  62. Popik, P. and Danysz, W. (1997) Inhibition of reinforcing effects of morphine and motivational aspects of naloxoneprecipitated opioid withdrawal by N-methyl-D-aspartate receptor antagonist, memantine. J. Pharmacol. Exp. Ther. 80, 854–865.

    Google Scholar 

  63. Popik, P., Mamczarz, J., Fraczek, M., Widla, M., Hesselink, M., and Danysz, W. (1998) Inhibition of reinforcing effects of morphine and naloxone-precipitated opioid withdrawal by novel glycine site and uncompetitive NMDA receptor antagonists. Neuropharmacology 37, 1033–1042.

    PubMed  CAS  Google Scholar 

  64. Wong, B. Y., Coulter, D. A., Choi, D. W., and Prince, D. A. (1988) Dextrophan and dextromethorphan, common antiussives, are antiepileptic and antagonize N-methyl-n-aspartate in brain slices. Neurosci. Lett. 85, 261–266.

    PubMed  CAS  Google Scholar 

  65. Franklin, P. H., and Murray, T. F. (1992) High affinity [3H]dextrorphan binding in rat brain is localized to a noncompetitive antagonist site of the activated N-methyl-D-aspartate receptor-cation channel. Mol. Pharmacol. 41, 134.

    PubMed  CAS  Google Scholar 

  66. Koyuncouglu, H., Gungor, M., Sagduyu, H., and Aricioglu, F. (1990) Suppression by ketamine and dextromoethorphan of precipitated abstinence syndrome in rats. Pharmacol. Biochem. Behay. 35, 829.

    Google Scholar 

  67. Farzin, D. (1999) Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice. Eur. J. Pharmacol. 377, 35–42.

    PubMed  CAS  Google Scholar 

  68. Koyuncouglu, H. and Saydam, B. (1990) The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. Int. J. Clin. Pharmacol. Ther. Toxicol. 28, 147.

    Google Scholar 

  69. Rosen, M. I., McMahon, T. J., Woods, S. W., Pearsall H. R., and Kosten, T. R. (1996) A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal. Eur. J. Pharmacol. 307, 251–257.

    PubMed  CAS  Google Scholar 

  70. Cornish, J. W., Herman, B. H., Ehrman, R. N., Robbins, S. J., Childress, A. R., Bead, V., et al. (2001) A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients. Drug Alcohol Depend., 61, 183–189.

    PubMed  CAS  Google Scholar 

  71. Curran, T., Abate, C., Cohen, D. R., Macgregor, P. E, Rauscher, F. J. 3d, Sonnenberg, J. L., (1990) Inducible proto-oncogene transcription factors: third messengers in the brain. Cold Spring Harb. Syml. Quant. Biol. 55, 225–234.

    CAS  Google Scholar 

  72. Morgan, J. I. and Curran, T. (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu. Rev. Neurosci. 14, 421–451.

    PubMed  CAS  Google Scholar 

  73. Sheng, M. and Greenberg, M. E. (1990) The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4, 477–485.

    PubMed  CAS  Google Scholar 

  74. Sonnenberg, J. L., Macgregor-Leon, P. F., Curran, T., and Morgan, J. I. (1989) Dynamic alterations occur in the levels and composition of transcription factor AP-1 complexes after seizure. Neuron, 3, 359–365.

    PubMed  CAS  Google Scholar 

  75. Hayward, M. D, Duman, R. S., and Nestler, E. J. (1990): Induction of the c-fos proto-oncogene during opiate withdrawal in the locus coeruleus and other regions of rat brain. Brain Res. 525, 256–266.

    PubMed  CAS  Google Scholar 

  76. Stometta, R. L., Norton, F. E., and Guyenet, P. G. (1993) Autonomic areas of rat brain exhibit increased Fos-like immunoreactivity during opiate withdrawal in rats. Brain Res. 624, 19–28.

    Google Scholar 

  77. Chahl, L. A., Leah, J., Herdegen, T., Trueman, L., and Lynch-Frame, A. M. (1996) Distribution of c-Fos in guinea-pig brain following morphine withdrawal. Brain Res. 717, 127–134.

    PubMed  CAS  Google Scholar 

  78. Rasmussen, K., Brodsky, M., and Inturrisi, C. E. (1995) NMDA antagonists and clonidine block c-fos expression during morphine withdrawal. Synapse 20, 68–74.

    PubMed  CAS  Google Scholar 

  79. Monaghan, D. T. and Cotman, C. W. (1985) Distribution of N-methyl-n-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J. Neurosci. 5, 2909–2919.

    PubMed  CAS  Google Scholar 

  80. Higgins, G. A., Nguyen, P., and Sellers, E. M. (1992) The NMDA antagonist dizocilpine (MK801) attenuates motivational as well as somatic aspects of naloxone precipitated opioid withdrawal. Life Sci. 50, PL167—PL172.

    Google Scholar 

  81. Kosten, T. A. (1994) Clonidine attenuates conditioned aversion produced by naloxone-precipitated opiate withdrawal. Eur. J. Pharm. 254, 59–63.

    CAS  Google Scholar 

  82. Kest, K., McLemore, G., Kao, B., and Inturrisi, C. E. (1997) The competitive a-amino-3-hydroxy-5-methylisoxazole-4propoinate receptor antagonist LY293558 attenuates and reverses analgesic tolerance to morphine but not to delta or kappa opioids. J. Pharmacol. Exp. Ther. 283, 1249–1255.

    PubMed  CAS  Google Scholar 

  83. McLemore, G. L., Kest, B., and Inturrisi, C. E. (1997) The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence. Brain Res. 778, 120–126.

    PubMed  CAS  Google Scholar 

  84. Carlezon, W. A., Rasmussen, K., and Nestler, E. J. (1999) AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine. Synapse 31, 256–262.

    PubMed  CAS  Google Scholar 

  85. Rasmussen, K. (1995) The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal. Neuropsychopharmacology 13, 295–300.

    PubMed  CAS  Google Scholar 

  86. Rasmussen, K., Kendrick, W. T., Kogan, J. H., and Aghajanian, G. K., (1996) A selective AMPA antagonist, LY293558, antagonizes morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal. Neuropsychopharmacology 15, 497–505.

    PubMed  CAS  Google Scholar 

  87. Taylor, J. R., Punch, L. J, and Elsworth, J. D. (1998) A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat. Psychopharmacology 138, 133–142.

    PubMed  CAS  Google Scholar 

  88. Monaghan, D. T., Yao, D., and Cotman, C. W. (1984) Distribution of [3H] AMPA binding sites in rat brain as determined by quantitative autoradiography. Brain Res. 324, 160–164.

    PubMed  CAS  Google Scholar 

  89. Young, A. B. and Fagg, G. E. (1990) Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharm. Sci. 11, 126–133.

    PubMed  CAS  Google Scholar 

  90. Davis, M. (1992) The role of the amygdala in fear and anxiety. Annu. Rev. Neurosci. 15, 353–373.

    PubMed  CAS  Google Scholar 

  91. Vizi, E. S., Mike, A., and Tarnawa, I. (1996) 2,3-Benzodiazepines (GYM 52466 and analogs): negative allosteric modulators of AMPA receptors. CNS Drug Rev. 2, 91–126.

    Google Scholar 

  92. Bleakman, D., Ballyk, B. A., Schoepp, D. D., Palmer, A. J., Bath, C. P, Sharpe, E. F., et al. (1996) Activity of 2,3-benzodiazepines at native rat and recombinant human glutamate receptors in vitro: stereospecificity and selectivity profiles. Neuropharmacology 35, 1689–1702.

    PubMed  CAS  Google Scholar 

  93. Bortolotto, Z. A., Clarke, V. R., Delany, C. M., Parry, M. C., Smolders, I., Vignes, M., et al. (1999) Kainate receptors are involved in synaptic plasticity. Nature 402, 297–301.

    PubMed  CAS  Google Scholar 

  94. Rasmussen, K. and Vandergriff, J. L. (1997) The selective AMPA antagonist LY300168 suppresses morphine-withdrawalinduced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal, Soc. Neurosci. Abstr. 23, 1201.

    Google Scholar 

  95. Simmons, R. A., Li, D. L., Hoo, K. H., Deverill, M., Ornstein, P. L., and Iyengar, S. (1998) Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat. Neuropharmacology 37, 25–36.

    PubMed  CAS  Google Scholar 

  96. Fundytus, M. E. and Coderre, T. J. (1994) Effect of activity at metabotropic, as well as ionotropic (NMDA), glutamate receptors on morphine dependence. Br. J Pharmacol. 113, 1215–1220.

    PubMed  CAS  Google Scholar 

  97. Fundytus, M. E., Ritchie, J., and Coderre, T. J. (1997) Attenuation of morphine withdrawal symptoms by subtype-selective metabotropic glutamate receptor antagonists. Br. J. Pharmacol. 120, 1015–1020.

    PubMed  CAS  Google Scholar 

  98. Fundytus, M. E. and Coderre, T. J. (1999) Opioid tolerance and dependence: a new model highlighting the role of metabotropic glutamate receptors. Pain Forum 8, 3–13.

    Google Scholar 

  99. Popik, P., Kozela, E., and Pilc, A. (2000) Selective agonist of group II glutamate metabotropic receptors, LY354740, inhibits tolerance to analgesic effects of morphine in mice. Br. J. Pharmacol. 130, 1425–1431.

    PubMed  CAS  Google Scholar 

  100. Klodzinska, A., Chojnacka, W. E., Palucha, A., Branski, P., Popik, P., and Pilc, A. (1999) Potential anti-anxiety and anti-addictive effects of LY354740. A selective group II glutamate metabotropic receptors agonist in animal models. Neuropharmacology 38, 1831–1839.

    PubMed  CAS  Google Scholar 

  101. Vandergriff, J. and Rasmussen, K. (1999) The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal. Neuropharmacology 38, 217–222.

    PubMed  CAS  Google Scholar 

  102. Dube, G. R. and Marshall, K. C. (1997) Modulation of excitatory synaptic transmission in locus coeruleus by multiple presynaptic metabotropic glutamate receptors. Neuroscience 80, 511–521.

    PubMed  CAS  Google Scholar 

  103. Battaglia, G., Monn, J. A., and Schoepp, D. D. (1997) In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats. Neurosci. Leu. 229, 161–164.

    CAS  Google Scholar 

  104. Salt, T. E. and Eaton, S. A. (1995) Distinct presynaptic metabotropic receptors for L-AP4 and CCG1 on gabaergic terminals: pharmacological evidence using novel alpha-methyl derivative mGluR antagonists. MAP4 and MCCG, in the rat thalamus in vivo. Neuroscience 65, 5–13.

    PubMed  CAS  Google Scholar 

  105. Schafthauser, H., Cartmell, J., Jakob-Rotne, R., and Mutel, V. (1997) Pharmacological characterization of metabotropic glutamate receptors linked to the inhibition of adenylate cyclase activity in rat striatal slices. Neuropharmacology 36, 933–940.

    Google Scholar 

  106. Nestler, E. J. (1996) Under siege: the brain on opiates. Neuron 16, 897–900.

    PubMed  CAS  Google Scholar 

  107. Nestler, E. J. and Aghajanian, G. K. (1997) Molecular and cellular basis of addiction. Science 278, 58–63.

    PubMed  CAS  Google Scholar 

  108. Ivanov, A. and Aston-Jones, G. (2001) Local opiate withdrawal in locus coeruleus neurons in vitro. J. Neurophysiol. 85, 2388–2397.

    PubMed  CAS  Google Scholar 

  109. Lane-Ladd, S. B., Pineda, J., Boundy, V. A., Pfeuffer, T., Krupinski, J., Aghajanian, G. K., et al. (1997) CREB (cAMP response element-binding protein) in the locus coeruleus: biochemical, physiological, and behavioral evidence for a role in opiate dependence. J. Neurosci. 17, 7890–7901.

    PubMed  CAS  Google Scholar 

  110. Punch, L. J., Self, D. W., Nestler, E. J., and Taylor J. R. (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.

    PubMed  CAS  Google Scholar 

  111. Petralia, R. S., Wang, Y. X., Niedzielski, A. S., and Wenthold, R. J. (1995) The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience 71, 949–976.

    Google Scholar 

  112. Schoepp, D. D., Johnson, B. G., Wright, R. A., Salhoff, C. R., Mayne, N. G., Wu, S., (1997) Ly354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Neuropharmacology 36, 1–11.

    PubMed  CAS  Google Scholar 

  113. Ohishi, H., Shigemoto, R., Nakanishi, S., and Mizuno, N. (1993a) Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J. Comp. Neurol. 335, 252–266.

    PubMed  CAS  Google Scholar 

  114. Ohishi, H., Shigemoto, R., Nakanishi, S., and Mizuno, N. (1993b) Distribution of the mRNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat. Neuroscience 53, 1009–1018.

    PubMed  CAS  Google Scholar 

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Authors
  1. Kurt Rasmussen PhD
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Editor information

Editors and Affiliations

  1. Clinical Medical Branch, Division of Treatment Research and Development, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Barbara H. Herman PhD

  2. Pharmacology, Integrative & Cellular Neurobiology Research Branch (PICNRB), Division of Neuroscience & Behavioral Research (DNBR), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Jerry Frankenheim PhD

  3. Treatment Research Branch, Division of Clinical and Prevention Research, National Institute on Drug Abuse (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA

    Raye Z. Litten PhD

  4. Division of Neuropharmacological Drug Products Center for Drug Evaluation and Research, Office of Drug Evaluation I, Food and Drug Administration, Rockville, MD, USA

    Philip H. Sheridan MD

  5. Laboratory of Molecular and Cellular Neurobiology, Division of Intramural Clinical and Biological Research, National Institute on Drug Abuse (NIAAA) National Institutes of Health (NIH), Bethesda, MD, USA

    Forrest F. Weight MD

  6. Division of Treatment Research and Development, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Steven R. Zukin MD

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© 2002 Springer Science+Business Media New York

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Rasmussen, K. (2002). Morphine Withdrawal as a State of Glutamate Hyperactivity. In: Herman, B.H., Frankenheim, J., Litten, R.Z., Sheridan, P.H., Weight, F.F., Zukin, S.R. (eds) Glutamate and Addiction. Contemporary Clinical Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-306-4_22

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  • DOI: https://doi.org/10.1007/978-1-59259-306-4_22

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-234-6

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