Skip to main content

Advertisement

SpringerLink
Log in

The neurobiology of opiate tolerance, dependence and sensitization: Mechanisms of NMDA receptor-dependent synaptic plasticity

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Long-term administration of opiates leads to changes in the effects of these drugs, including tolerance, sensitization and physical dependence. There is, as yet, incomplete understanding of the neural mechanisms that underlie these phenomena. Tolerance, sensitization and physical dependence can be considered adaptive processes similar to other experience-dependent changes in the brain, such as learning and neural development. There is considerable evidence demonstrating that N-methyl-d-aspartate (NMDA) receptors and downstream signaling cascades may have an important role in different forms of experience-dependent changes in the brain and behavior. This review will explore evidence indicating that NMDA receptors and downstream messengers may be involved in opiate tolerance, sensitization and physical dependence. This evidence has been used to develop a cellular model of NMDA receptor/opiate interactions. According to this model, mu opioid receptor stimulation leads to a protein kinase C-mediated activation of NMDA receptors. Activation of NMDA receptors leads to influx of calcium and activation of calcium-dependent processes. These calcium-dependent processes have the ability to produce critical changes in opioid-responsive neurons, including inhibition of opioid receptor/second messenger coupling. This model is similar to cellular models of learning and neural development in which NMDA receptors have a central role. Together, the evidence suggests that the mechanisms that underlie changes in the brain and behavior produced by long-term opiate use may be similar to other central nervous system adaptations. The experimental findings and the resulting model may have implications for the treatment of pain and addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abel, T. and Kandel, E. (1998) “Positive and negative regulatory mechanisms that mediate long-term memory storage”, Brain Res. Rev. 26, 360–378.

    Article  PubMed  CAS  Google Scholar 

  • Abel, T. and Lattal, K.M. (2001) “Molecular mechanisms of memory acquisition, consolidation and retrieval”, Curr. Opin. Neurobiol. 11, 180–187.

    Article  PubMed  CAS  Google Scholar 

  • Abraham, W.C. and Bear, M.F. (1996) “Metaplasticity: the plasticity of synaptic plasticity”, Trends Neurosci. 19, 126–130.

    Article  PubMed  CAS  Google Scholar 

  • Adams, J.P., Roberson, E.D., English, J.D., Selcher, J.C. and Sweatt, J.D. (2000) “MAPK regulation of gene expression in the central nervous system”, Acta Neurobiol. Exp. 60, 377–394.

    CAS  Google Scholar 

  • Ai, W., Gong, J. and Yu, L. (1999) “MAP kinase activation by mu opioid receptor involves phosphatidylinositol 3-kinase but not the cAMP/PKA pathway”, FEBS Lett. 456, 196–200.

    Article  PubMed  CAS  Google Scholar 

  • Allen, R.M. and Dykstra, L.A. (1999) “The competitive NMDA receptor antagonist LY235959 modulates the progression of morphine tolerance in rats”, Psychopharmacology 142, 209–214.

    Article  PubMed  CAS  Google Scholar 

  • Artola, A. and Singer, W. (1993) “Long-term depression of excitatory synaptic transmission and its relationship to long-term depression”, Trends Neurosci. 16, 480–487.

    Article  PubMed  CAS  Google Scholar 

  • Babbini, M. and Davis, W.M. (1972) “Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment”, Br. J. Pharmacol. 46, 213–224.

    PubMed  CAS  Google Scholar 

  • Babbini, M., Gaiardi, M. and Bartoletti, M. (1975) “Persistence of chronic morphine effects upon activity in rats 8 months after ceasing the treatment”, Neuropharmacology 14, 611–614.

    Article  PubMed  CAS  Google Scholar 

  • Babey, A.M., Kolesnikov, Y., Cheng, J., Inturrisi, C.E., Trifilletti, R.R. and Pasternak, G.W. (1994), “Nitric oxide and opioid tolerance”, Neuropharmacology 33, 1463–1470.

    Article  PubMed  CAS  Google Scholar 

  • Bartoletti, M., Gairdi, M., Gubellini, C., Bacchi, A. and Babbini, M. (1987) “Previous treatment with morphine and sensitization to the excitatory actions of opiates: dose-effect relationship”, Neuropharmacology 26, 115–119.

    Article  PubMed  CAS  Google Scholar 

  • Bear, M.F. (1996) “NMDA-receptor-dependent synaptic plasticity in the visual cortex”, Prog. Brain Res. 108, 205–218.

    Article  PubMed  CAS  Google Scholar 

  • Bear, M.F. and Malenka, R.C. (1994) “Synaptic plasticity: LTP and LTD”, Curr. Opin. Neurobiol. 4, 389–399.

    Article  PubMed  CAS  Google Scholar 

  • Bear, M.F. and Rittenhouse, C.D. (1999) “Molecular basis for induction of ocular dominance plasticity”, J. Neurobiol. 41, 83.

    Article  PubMed  CAS  Google Scholar 

  • Befort, K., Filliol, D., Decaillot, F.M., Gaveriaux-Ruff, C., Hoehe, M.R. and Kieffer, B.L. (2001) “A single nucleotide polymorphic mutation in the human [micro]-opioid receptor severely impairs receptor signaling”, J. Biol. Chem. 276, 3130–3137.

    Article  PubMed  CAS  Google Scholar 

  • Bell, R.F. (1999) “Low-dose subcutaneous ketamine infusion and morphine tolerance”, Pain 83, 101–103.

    Article  PubMed  CAS  Google Scholar 

  • Berhow, M.T., Hiroi, N. and Nestler, E.J. (1996) “Regulation of ERK (extracellular signal regulated kinase), part of the neurotrophin signal transduction cascade, in the rat mesolimbic dopamine system by chronic exposure to morphine or cocaine”, J. Neurosci. 16, 1407–1415.

    Google Scholar 

  • Bespalov, A.Y., Balster, R.L. and Beardsley, P.M. (1999) “N-methyl-D-aspartate receptor antagonists and the development of tolerance to the discriminitive stimulus effects of morphine in rats”, J. Pharmacol. Exp. Ther. 290, 20–27.

    PubMed  CAS  Google Scholar 

  • Bespalov, A.Y., Zvartau, E.E., Krupitsky, E.M., Mosolov, D.V. and Burakov, A.M. (2001) “A pilot study of memantine for the treatment of heroin dependence”, Drug. Alc. Depend 63(Suppl. 1), S14.

    Google Scholar 

  • Bhargava, H.N. (1994) “Diversity of agents that modify opioid tolerance, physical dependence, abstinence syndrome, and self-administrative behavior”, Pharmacol. Rev. 46, 293–324.

    PubMed  CAS  Google Scholar 

  • Bhargava, H.N. (1995) “Attenuation of tolerance to, and physical dependence on, morphine in the rat by inhibition of nitric oxide synthase”, Gen. Pharmacol. 26, 1049–1053.

    PubMed  CAS  Google Scholar 

  • Bhargava, H.N. and Matwyshyn, G.A. (1993) “Dizocilpine (MK-801) blocks tolerance to the analgesic but not to the hyperthermic effect of morphine in the rat”, Pharmacology 47, 344–350.

    Article  PubMed  CAS  Google Scholar 

  • Bhargava, H.N. and Zhao, G.M. (1996) “Effect of nitric oxide synthase inhibition on tolerance to the analgesic action of D-Pen2, D-Pen5 enkephalin and morphine in the mouse”, Neuropeptides 30, 219–223.

    Article  PubMed  CAS  Google Scholar 

  • Bhargava, H.N., Cao, Y.J. and Zhao, G.M. (1997) “Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen2, D-Pen5] enkephalin in mice”, Peptides 18, 797–800.

    Article  PubMed  CAS  Google Scholar 

  • Bilecki, W. and Przewlocki, R. (2000) “Effect of opioids on Ca2+/cAMP responsive element binding protein”, Acta Neurobiol. Exp. 60, 557–567.

    CAS  Google Scholar 

  • Bilsky, E.J., Bernstein, R.N., Wang, Z., Sadee, W. and Porreca, F. (1996) “Effects of naloxone and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 and the protein kinase inhibitors H7 and H8 on acute morphine dependence and antinociceptive tolerance in mice”, J. Pharmacol. Exp. Ther. 277, 484–490.

    PubMed  CAS  Google Scholar 

  • Bisaga, A. and Popik, P. (2000) “In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-D-aspartate (NMDA) antagonists”, Drug. Alc. Depend. 59, 1–15.

    Article  CAS  Google Scholar 

  • Bisaga, A., Gianelli, P. and Popik, P. (1997) “Opiate withdrawal and dextromethorphan”, Am. J. Psychiatry 154, 584.

    PubMed  CAS  Google Scholar 

  • Blendy, J.A. and Maldonado, R. (1998) “Genetic analysis of drug addiction: the role of cAMP response element binding protein”, J. Mol. Med. 76, 104–110.

    Article  PubMed  CAS  Google Scholar 

  • Bond, C., LaForge, K.S., Tian, M., Melia, D., Zhang, S., Borg, L., Gong, J., Schluger, J., Strong, J.A., Leal, S.M., Tischfield, J.A., Kreek, M.J. and Yu, L. (1998) “Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction”, Proc. Natl. Acad. Sci. USA 95, 9608–9613.

    Article  PubMed  CAS  Google Scholar 

  • Brady, L.S. and Holtzman, S.G. (1981) “Locomotor behavior in morphine-dependent and post-dependent rats”, Pharmacol. Biochem. Behav. 14, 361–370.

    Article  PubMed  CAS  Google Scholar 

  • Bruggemann, I., Schulz, S., Wiborny, D. and Hollt, V. (2000) “Colocalization of the mu-opioid receptor and calcium/calmodulin-dependent kinase II in distinct pain-processing brain regions”, Mol. Brain Res. 85, 239–250.

    Article  PubMed  CAS  Google Scholar 

  • Cai, Y.-C., Ma, L., Fan, G.-H., Zhao, J., Jiang, L.-Z. and Pei, G. (1997) “Activation of N-methyl-D-aspartate receptor attenuates acute responsiveness of δ-opioid receptors”, Mol. Pharmacol. 51, 583–587.

    PubMed  CAS  Google Scholar 

  • Chakrabarti, S., Oppermann, M. and Gintzler, A.R. (2001) “Chronic morphine induces the concomitant phosphorylation and altered association of multiple signaling proteins: a novel mechanism for modulating cell signaling”, Proc. Natl. Acad. Sci. USA 98, 4209–4214.

    Article  PubMed  CAS  Google Scholar 

  • Chen, L. and Huang, L.Y. (1991) “Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid”, Neuron 7, 319–326.

    Article  PubMed  Google Scholar 

  • Chen, L. and Huang, L.Y. (1992) “Protein kinase C reduces Mg++ block of NMDA-receptor channels as a mechanism of modulation”, Nature 356, 521–523.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y. and Yu, L. (1994) “Differential regulation by cAMP-dependent protein kinase and protein kinase C of the μ opioid receptor coupling to a G protein-activated K+ channel”, J. Biol. Chem. 269, 7839–7842.

    PubMed  CAS  Google Scholar 

  • Chevlen, E. (2000) “Morphine with dextromethorphan: conversion from other opioid analgesics”, J. Pain Symptom. Manage. 19, S42-S49.

    Article  PubMed  CAS  Google Scholar 

  • Childers, S. (1993) “Opioid receptor-coupled second messenger systems”, In: Akil, H. and Simon, E.J., eds, Opioids I (Springer, New York), pp. 189–216.

    Google Scholar 

  • Coderre, T.J., Katz, J., Vaccarino, A.L. and Melzack, R. (1993) “Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence”, Pain 53, 259–285.

    Article  Google Scholar 

  • Collingridge, G.L. and Lester, R.A.J. (1989) “Excitatory amino acid receptors in the vertebrate central nervous system”, Pharmacol. Rev. 41, 143–210.

    PubMed  CAS  Google Scholar 

  • Collingridge, G.L. and Watkins, J.C. (1994) The NMDA Receptor (Oxford University Press, New York).

    Google Scholar 

  • Commons, K.G., van Bockstaele, E.J. and Pfaff, D.W. (1999) “Frequent colocalization of mu opioid and NMDA-type glutamate receptors at postsynaptic sites in periaqueductal gray neurons”, J. Comp. Neurol. 408 549–559.

    Article  PubMed  CAS  Google Scholar 

  • Conn, P.J. and Pin, J.-P. (1997) “Pharmacology and functions of metabotropic glutamate receptors”, Annu. Rev. Pharmacol. Toxicol. 37, 205–237.

    Article  PubMed  CAS  Google Scholar 

  • Contestabile, A. (2000) “Roles of NMDA receptor activity and nitric oxide production in brain development”, Brain Res. Rev. 32, 476–509.

    Article  PubMed  CAS  Google Scholar 

  • Cox, B.M. (1991) “Molecular and cellular mechanisms in opioid tolerance”, In: Basbaum, A.I. and Besson, J.-M., eds, Towards a New Pharmacotherapy of Pain (Wiley, New York), pp. 137–156.

    Google Scholar 

  • Cox, B.M. and Werling, L.L. (1991) “Opioid tolerance and dependence”, In: Pratt, J.A., eds, The Biological Basis of Drug Tolerance and Dependence (Academic Press, San Diego), pp. 199–229.

    Google Scholar 

  • Crain, S.M. and Shen, K.-F. (1990) “Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons”, Trends Pharmacol. Sci. 11, 77–81.

    Article  PubMed  CAS  Google Scholar 

  • Crain, S.M. and Shen, K.-F. (1996) “Modulatory effects of Gs-coupled excitatory opioid receptor functions on opioid analgesia, tolerance and dependence”, Neurochem. Res. 21, 1347–1351.

    Article  PubMed  CAS  Google Scholar 

  • Crain, S.M. and Shen, K.-F. (1998) “Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions”, Trends Pharmacol. Sci. 19, 358–365.

    Article  PubMed  CAS  Google Scholar 

  • Crain, S.M. and Shen, K.F. (2000) “Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability”, Pain 84, 121–131.

    Article  PubMed  CAS  Google Scholar 

  • Crepel, V., Congar, P., Aniksztejn, L., Gozlan, H., Hammond, C. and Ben-Ari, Y. (1998) “Synaptic plasticity in ischemia: role of NMDA receptors”, Prog. Brain Res. 116, 273–285.

    Article  PubMed  CAS  Google Scholar 

  • Danysz, W. and Parsons, C.G. (1998) “Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications”, Pharmacol. Rev. 50, 597–664.

    PubMed  CAS  Google Scholar 

  • Dash, P., Karl, K., Colicos, M., Prywes, R. and Kandel, E. (1991) “cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase”, Proc. Natl. Acad. Sci. USA 88, 5061–5065.

    Article  PubMed  CAS  Google Scholar 

  • Davis, M., Falls, W.A., Campeau, S. and Kim, M. (1993) “Fear-potentiated startle: a neural and pharmacological analysis”, Behav. Brain Res. 58, 175–198.

    Article  PubMed  CAS  Google Scholar 

  • De Blasi, A., Conn, P.J., Pin, J.-P. and Nicoletti, F. (2001) “Molecular determinants of metabotropic glutamate receptor signaling”, Trends Pharmacol. Sci. 22, 114–120.

    Article  PubMed  Google Scholar 

  • De Cesare, D., Fimia, G.M. and Sassone-Corsi, P. (1999) “Signaling routes to CREM and CREB: plasticity in transcriptional activation”, Trends Biochem. Sci. 24, 281–285.

    Article  PubMed  Google Scholar 

  • Dickenson, A.H. (1995) “Central acute pain mechanisms”, Ann. Med. 27, 223–227.

    Article  PubMed  CAS  Google Scholar 

  • Dingledine, R., Borges, K., Bowie, D. and Traynelis, S.F. (1999) “The glutamate receptor ion channels”, Pharmacol. Rev. 51, 7–61.

    PubMed  CAS  Google Scholar 

  • Domino, E.F., Vaski, M.R. and Wilson, A.E. (1976) “Mixed depressant and stimulant actions of morphine and their relationship to brain acetylcholine”, Life Sci. 18, 361–376.

    Article  PubMed  CAS  Google Scholar 

  • Duaux, E., Krebs, M.O., Loo, H. and Poirier, M.F. (2000) “Genetic vulnerability to drug abuse”, Eur. Psychiatry 15, 109–114.

    Article  PubMed  CAS  Google Scholar 

  • Dunbar, S. and Yaksh, T.L. (1996) “Effect of spinal infusion of L-NAME, a nitric oxide synthase inhibitor, on spinal tolerance and dependence induced by chronic intrathecal morphine in the rat”, Neurosci. Lett. 207, 33–36.

    Article  PubMed  CAS  Google Scholar 

  • 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, 69–75.

    Article  PubMed  CAS  Google Scholar 

  • Fairbanks, C.A. and Wilcox, G.L. (1997) “Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance”, J. Pharmacol. Exp. Ther. 282, 1408–1417.

    PubMed  CAS  Google Scholar 

  • Fan, G.-H., Zhao, J., Wu, Y.L., Lou, L.G., Zhang, Z., Jing, Q., Ma, L. and Pei, G. (1998) “N-Methyl-d-aspartate attenuates opioid receptor-mediated G protein activation and this process involves protein kinase C”, Mol. Pharmacol. 53, 684–690.

    PubMed  CAS  Google Scholar 

  • Fan, G.-H., Wang, L.-Z., Qiu, H.-C., Ma, L. and Pei, G. (1999) “Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence”, Mol. Pharmacol. 56, 39–45.

    PubMed  CAS  Google Scholar 

  • Frank, D.A. and Greenberg, M.E. (1994) “CREB: a mediator of long-term memory from mollusks to mammals”, Cell, 79.

  • Fukuda, K., Kato, S., Morikawa, H., Shoda, T. and Mori, K. (1996) “Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells”, J. Neurochem. 67, 1309–1316.

    PubMed  CAS  Google Scholar 

  • Fundytus, M.E. and Coderre, T.J. (1996) “Chronic inhibition of intracellular Ca2+ release or protein kinase C activation significantly reduces the development of morphine dependence”, Eur. J. Pharmacol. 300, 173–181.

    Article  PubMed  CAS  Google Scholar 

  • Garcia, M.M. and Harlan, R.E. (1993) “Chronic morphine increases calbindin D28k in rat striatum: possible NMDA receptor involvement”, Neuroreport 25, 65–68.

    Google Scholar 

  • Gelernter, J., Kranzler, H. and Cubells, J. (1999) “Genetics of two mu opioid receptor gene (OPRM1) exon I polymorphisms: population studies, and allele frequencies in alcohol-and drug-dependent subjects”, Mol. Psychiatry 4, 476–483.

    Article  PubMed  CAS  Google Scholar 

  • Gintzler, A.R. and Chakrabarti, S. (2000) “Opioid tolerance and the emergence of new opioid receptor-coupled signaling”, Mol. Neurobiol. 21, 21–33.

    Article  PubMed  CAS  Google Scholar 

  • Gracy, K.N., Svingos, A.L. and Pickel, V.M. (1997) “Dual ultrastructural localization of mu-opioid receptors and NMDA-type glutamate receptors in the shell of the rat nucleus accumbens”, J. Neurosci. 17, 4839–4848.

    PubMed  CAS  Google Scholar 

  • Granados-Soto, V., Kalcheva, I., Hua, X., Newton, A. and Yaksh, T.L. (2000) “Spinal PKC activity and expression: role in tolerance produced by continuous spinal morphine infusion”, Pain 85, 395–404.

    Article  PubMed  CAS  Google Scholar 

  • Grassi, S. and Pettorossi, V.E. (2001) “Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messngers in rat brainstem slices”, Prog. Neurobiol. 64, 527–553.

    Article  PubMed  CAS  Google Scholar 

  • Guitart, X., Thompson, M.A., Mirante, C.K., Greenberg, M.E. and Nestler, E.J. (1992) “Regulation of cyclic AMP response element-binding protein (CREB) phosphorylation by acute and chronic morphine in the rat locus coeruleus”, J. Neurochem. 58, 1168–1171.

    Article  PubMed  CAS  Google Scholar 

  • Gutstein, H.B., Rubie, E.A., Mansour, A., Akil, H. and Woodgett, J.R. (1997) “Opioid effects on mitogen-activated protein kinase signaling cascades”, Anesthesiology 87, 1118–1126.

    Article  PubMed  CAS  Google Scholar 

  • Guzowski, J.E. and McGaugh, J.L. (1997) “Antisense oligodeoxynucleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training”, Proc. Natl. Acad. Sci. USA 94, 2693–2698.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, L.M., Kastin, A.J. and Zadina, J.E. (1998) “Opiate tolerance and dependence: Receptors, G-proteins, and antiopiates”, Peptides 19, 1603–1630.

    Article  PubMed  CAS  Google Scholar 

  • 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, 269–293.

    Article  PubMed  CAS  Google Scholar 

  • Hess, D.T., Lin, L.H., Freeman, J.A. and Norden, J.J. (1994) “Modification of cysteine residues within G(0) and other neuronal proteins by exposure to nitric oxide”, Neuropharmacology 33, 1283–1292.

    Article  PubMed  CAS  Google Scholar 

  • Highfield, D.A. and Grant, S. (1998) “Ng-nitro-l-arginine, an NOS inhibitor, reduces tolerance to morphine in the rat locus coeruleus”, Synapse 29, 233–239.

    Article  PubMed  CAS  Google Scholar 

  • Huang, J., Wang, H. and Pickel, V.M. (2000) “Rostrocaudal variation in targeting of N-methyl-d-aspartate and mu-opioid receptors in the rat medial nucleus of the solitary tract”, J. Comp. Neurol. 421, 400–411.

    Article  PubMed  CAS  Google Scholar 

  • Iijima, Y., Asami, T. and Kuribara, H. (1996) “Modification by MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, of morphine sensitization: evaluation by ambulation in mice”, Jpn. J. Psychopharmacol. 16, 11–18.

    CAS  Google Scholar 

  • Impey, S., Obrietan, K. and Storm, D.R. (1999) “Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity”, Neuron 23, 11–14.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, M. and Ueda, H. (2000) “Protein kinase C-mediated acute tolerance to peripheral mu-opioid analgesia in the bradykinin-nociception test in mice”, J. Pharmacol. Exp. Ther. 293, 662–669.

    PubMed  CAS  Google Scholar 

  • Inturrisi, C.E. (1997) “Preclinical evidence for a role of glutamatergic systems in opioid tolerance and dependence”, Semin. Neurosci. 9, 110–119.

    Article  CAS  Google Scholar 

  • Jeziorski, M., White, F.J. and Wolf, M.E. (1994) “MK-801 prevents the development of behavioral senstization during repeated morphine administration”, Synapse 16, 137–147.

    Article  PubMed  CAS  Google Scholar 

  • Ji, R.R. and Woolf, C.J. (2001) “Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain”, Neurobiol. Dis. 8, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Jordan, B. and Devi, L.A. (1998) “Molecular mechanisms of opioid receptor signal transduction”, Br. J. Anaesth. 81, 12–19.

    PubMed  CAS  Google Scholar 

  • Josselyn, S.A., Shi, C., Carlezon, Jr, W.A., Neve, R.L., Nestler, E.J. and Davis, M. (2001) “Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala”, J. Neurosci. 21, 2404–2412.

    PubMed  CAS  Google Scholar 

  • Kalivas, P.W. (1995) “Interactions between dopamine and excitatory amino acids in behavioral sensitization to psychostimulants”, Drug. Alcohol Depend. 37, 95–100.

    Article  PubMed  CAS  Google Scholar 

  • Katz, N.P. (2000) “MorphiDex (MS:DM) double-blind, multiple-dose studies in chronic pain patients”, J. Pain Symptom. Manage. 19, S37-S41.

    Article  PubMed  CAS  Google Scholar 

  • Kissin, I., Bright, C.A. and Bradley, Jr., E.L. (2000) “Acute tolerance to continuously infused alfentanil: the role of cholecystokinin and N-methyl-d-aspartate-nitric oxide systems”, Anesth. Analg. 91, 110–116.

    Article  PubMed  CAS  Google Scholar 

  • Koch, T., Kroslak, T., Mayer, P., Raulf, E. and Hollt, V. (1997) “Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonist-mediated desensitization”, J. Neurochem. 69, 1767–1770.

    PubMed  CAS  Google Scholar 

  • Kolesnikov, Y.A., Pick, C.G. and Pasternak, G.W. (1992) “NG-nitro-l-arginine prevents morphine tolerance”, Eur. J. Pharmacol. 221, 399–400.

    Article  PubMed  CAS  Google Scholar 

  • Kolesnikov, Y.A., Pick, C.G., Ciszewska, G. and Pasternak, G.W. (1993) “Blockade of tolerance to morphine but not to k opioids by a nitric oxide synthase inhibitor”, Proc. Natl. Acad. Sci. USA 90, 5162–5166.

    Article  PubMed  CAS  Google Scholar 

  • Kolesnikov, Y., Maccechini, M.L. and Pasternak, G.W. (1994) “1-Aminocyclopropane carboxylic acid (ACPC) prevents mu and delta opioid tolerance”, Life Sci. 55, 1393–1398.

    Article  PubMed  CAS  Google Scholar 

  • Kolesnikov, Y., Jain, S., Wilson, R. and Pasternak, G.W. (1998) “Lack of morphine and enkephalin tolerance in 129/SvEv mice: evidence for a NMDA receptor defect”, J. Pharmacol. Exp. Ther. 284, 455–459.

    PubMed  CAS  Google Scholar 

  • Kolesnikov, Y.A. and Pasternak, G.W. (1999a) “Peripheral blockade of topical morphine tolerance by ketamine”, Eur. J. Pharmacol. 374, R1-R2.

    Article  PubMed  CAS  Google Scholar 

  • Kolesnikov, Y.A. and Pasternak, G.W. (1999b) “Topical opioids in mice: analgesia and reversal of tolerance by a topical N-methyl-d-aspartate antagonist”, J. Pharmacol. Exp. Ther. 290, 247–252.

    PubMed  CAS  Google Scholar 

  • Koob, G.F. and Le Moal, M. (1997) “Drug abuse: hedonic homeostatic dysregulation”, Science 278, 52–58.

    Article  PubMed  CAS  Google Scholar 

  • Koob, G.F. and Le Moal, M. (2001) “Drug addiction, dysregulation of reward, and allostasis”, Neuropsychopharmacology 24, 97–129.

    Article  PubMed  CAS  Google Scholar 

  • Kosten, T.A. and Bombace, J.C. (2000) “Prior and delayed applications of dizocilpine or ethanol alter locomotor sensitization to morphine”, Brain Res. 878, 20–31.

    Article  PubMed  CAS  Google Scholar 

  • Koyuncuoglu, H. (1995) “The combination of tizanidine markedly improves the treatment with dextromethorphan of heroin addicted outpatients”, Int. J. Clin. Pharmacol. Ther. 33, 13–19.

    PubMed  CAS  Google Scholar 

  • Koyuncuoglu, 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. 28, 147–452.

    CAS  Google Scholar 

  • Kramer, H.K. and Simon, E.J. (2000) “mu and delta-opioid receptor agonists induce mitogen-activated protein kinase (MAPK) activation in the absence of receptor internalization”, Neuropharmacology 39, 1707–1719.

    Article  PubMed  CAS  Google Scholar 

  • LaForge, K.S., Shick, V., Spangler, R., Proudnikov, D., Yuferov, V., Lysov, Y., Mirzabekov, A. and Kreek, M.J. (2000) “Detection of single nucleotide polymorphisms of the human mu opioid receptor gene by hybridization or single nucleotide extension on custom oligonucleotide gelpad microchips: potential in studies of addiction”, Am. J. Med. Genet. 96, 604–615.

    Article  PubMed  CAS  Google Scholar 

  • Lane-Ladd, S.B., Pineda, J., Boundy, V.A., Pfeuffer, T., Krupinski, J., Aghajanian, G.K. and Nestler, E.J. (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 

  • Law, P.-Y. and Loh, H.H. (1999) “Regulation of opioid receptor activities”, J. Pharmacol. Exp. Ther. 289, 607–624.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Wong, Y.H. and Loh, H.H. (2000) “Molecular mechanisms and regulation of opioid receptor signalling,” Annu. Rev. Pharmacol. Toxicol. 40, 389–430.

    Article  PubMed  CAS  Google Scholar 

  • Le Guen, S., Catheline, G. and Besson, J.-M. (1999) “Effects of NMDA receptor antagonists on morphine tolerance: a c-Fos study in the lumbar spinal cord of the rat”, Eur. J. Pharmacol. 373, 1–11.

    Article  PubMed  Google Scholar 

  • Li, L.Y. and Chang, K.J. (1996) “The stimulatory effect of opioids on mitogen-activated protein kinase in Chinese hamster ovary cells transfected to express mu-opioid receptors”, Mol. Pharmacol. 50, 599–602.

    PubMed  CAS  Google Scholar 

  • Li, X. and Clark, J.D. (1999) “Morphine tolerance and transcription factor expression in mouse spinal cord tissue”, Neurosci. Lett. 272, 79–82.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y. and Roerig, S.C. (1999) “Alteration of spinal protein kinase C expression and kinetics in morphine, but not clonidine, tolerance”, Biochem. Pharmacol. 58, 493–501.

    Article  PubMed  CAS  Google Scholar 

  • Livezey, R.T., Pearce, L.B. and Kornetsky, C. (1995) “The effect of MK-801 and SCH23390 on the expression and sensitization of morphine-induced oral stereotypy”, Brain Res. 692, 93–98.

    Article  PubMed  CAS  Google Scholar 

  • Lou, L., Zhou, T., Wang, P. and Pei, G. (1999) “Modulation of Ca2+/calmodulin-dependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of alpha and beta isoforms”, Mol. Pharmacol. 55, 557–563.

    PubMed  CAS  Google Scholar 

  • Lu, L., Zeng, S., Liu, D. and Ceng, X. (2000) “Inhibition of the amygdala and hippocampal calcium/calmodulin-dependent protein kinase II attenuates the dependence and relapse to morphine differently in rats”, Neurosci. Lett. 291, 191–195.

    Article  PubMed  CAS  Google Scholar 

  • Lue, W.M., Su, M.T., Lin, W.B. and Tao, P.L. (1999) “The role of nitric oxide in the development of morphine tolerance in rat hippocampal slices”, Eur. J. Pharmacol. 383, 129–135.

    Article  PubMed  CAS  Google Scholar 

  • Lutfy, K., Doan, P. and Weber, E. (1999) “ACEA-1328 a NMDA receptor/glycine site antagonist, acutely potentiates antinociception and chronically attenuates tolerance induced by morphine”, Pharmacol. Res. 40, 435–442.

    Article  PubMed  CAS  Google Scholar 

  • Majeed, N.H., Przewlocka, B., Machelska, H. and Przewlocki, R. (1994) “Inhibition of nitric oxide synthase attenuates the development of morphine tolerance and dependence in mice”, Neuropharmacology 33, 189–192.

    Article  PubMed  CAS  Google Scholar 

  • Makimura, M., Sugimoto, H., Shinomiya, K., Kabasawa, Y. and Fukuda, H. (1996) “Inhibitory effect of the NMDA receptor antagonist, dizocilpine (MK-801), on the development of morphine dependence”, J. Toxicol. Sci. 21, 135–141.

    PubMed  CAS  Google Scholar 

  • Makimura, M., Iwai, M., Sugimoto, H. and Fukuda, H. (1997) “Effect of NMDA receptor antagonists on protein kinase activated by chronic morphine treatment”, J. Toxicol. Sci. 22, 59–66.

    Google Scholar 

  • Maldonado, R., Blendy, J.A., Tzavara, E., Gass, P., Roques, B.P., Hanoune, J. and Schutz, G. (1996) “Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB”, Science 273, 657–659.

    Article  PubMed  CAS  Google Scholar 

  • Malenka, R.C. and Nicoll, R.A. (1993) “NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms”, Trends Neurosci. 16, 521–527.

    Article  PubMed  CAS  Google Scholar 

  • Malenka, R.C. and Nicoll, R.A. (1999) “Long-term potentiation—a decade of progress?”, Science 285, 1870–1874.

    Article  PubMed  CAS  Google Scholar 

  • Mao, J. (1999) “NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity”, Brain Res. Rev. 30, 289–304.

    Article  PubMed  CAS  Google Scholar 

  • Mao, J. and Ji, R.R. (2001) “Induction of neuronal apoptosis following the induction of opiate tolerance”, Soc. Neurosci. Abstr. 27, Abstract #616.612.

  • Mao, J., Price, D.D. and Mayer, D.J. (1994) “Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C”, J. Neurosci. 14, 2301–2312.

    PubMed  CAS  Google Scholar 

  • Mao, J., Price, D.D. and Mayer, D.J. (1995a) “Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions”, Pain 62, 259–274.

    Article  PubMed  CAS  Google Scholar 

  • Mao, J., Price, D.D., Phillips, L.L., Lu, J. and Mayer, D.J. (1995b) “Increases in protein kinase C immunoreactivity in the spinal cord of rats associated with tolerance to the analgesic effects of morphine”, Brain Res. 677, 257–267.

    Article  PubMed  CAS  Google Scholar 

  • Marek, P., Ben-Eliyahu, S., Gold, M. and Liebeskind, J.C. (1991) “Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat”, Brain Res. 547, 77–81.

    Article  PubMed  CAS  Google Scholar 

  • Martin, G., Nie, Z. and Siggins, G.R. (1997) “mu-Opioid receptors modulate NMDA receptor-mediated responses in nucleus accumbens neurons”, J. Neurosci. 17, 11–22.

    PubMed  CAS  Google Scholar 

  • Martin, G., Ahmed, S.H., Blank, T., Spiess, J., Koob, G.F. and Siggins, G.R. (1999a) “Chronic morphine treatment alters NMDA receptor-mediated synaptic transmission in the nucleus accumbens”, J. Neurosci. 19, 9081–9089.

    PubMed  CAS  Google Scholar 

  • Martin, G., Przewlocki, R. and Siggins, G.R. (1999b) “Chronic morphine treatment selectively augments metabotropic glutamate receptor-induced inhibition of N-methyl-d-aspartate receptor-mediated neurotransmission in nucleus accumbens”, J. Pharmacol. Exp. Ther. 288, 30–35.

    PubMed  CAS  Google Scholar 

  • Mayer, D.J. and Mao, J. (1999) “Mechanisms of opioid tolerance: a current view of cellular mechanisms”, Pain Forum 8, 14–18.

    Google Scholar 

  • Mayer, D.J., Mao, J. and Price, D.D. (1995a) “The association of neuropathic pain, morphine tolerance and dependence, and the translocation of protein kinase C”, NIDA Res. Monogr. 147, 269–298.

    PubMed  CAS  Google Scholar 

  • Mayer, D.J., Mao, J. and Price, D.D. (1995b) “The development of morphine tolerance and dependence is associated with translocation of protein kinase C”, Pain 61, 365–374.

    Article  PubMed  CAS  Google Scholar 

  • Mayer, D.J., Mao, J., Holt, J. and Price, D.D. (1999) “Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions”, Proc. Natl Acad. Sci. USA 96, 7731–7736.

    Article  PubMed  CAS  Google Scholar 

  • Mayford, M. and Kandel, E.R. (1999) “Genetic approaches to memory storage”, Trends Genetics 15, 463–470.

    Article  CAS  Google Scholar 

  • McDonald, J.W. and Johnston, M.W. (1990) “Physiological and pathophysiological roles of excitatory amino acids during central nervous system development”, Brain Res. Rev. 15, 41–70.

    Article  PubMed  Google Scholar 

  • McGaugh, J.L. and Izquierdo, I. (2000) “The contribution of pharmacology to research on the mechanisms of memory formation”, Trends Pharmacol. Sci. 21, 208–210.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, S.B., Lewin, G.R. and Wall, P.D. (1993) “Central hyperexcitability triggered by noxious inputs”, Curr. Opin. Neurobiol. 3, 602–610.

    Article  PubMed  CAS  Google Scholar 

  • Mestek, A., Hurley, J.H., Bye, L.S., Campbell, A.D., Chen, Y., Tian, M., Liu, J., Schulman, H. and Yu, L. (1995) “The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C”, J. Neurosci. 15, 2396–2406.

    PubMed  CAS  Google Scholar 

  • Michaelis, E.K. (1998) “Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging”, Prog. Neurobiol. 54, 369–415.

    Article  PubMed  CAS  Google Scholar 

  • Morris, R.G.M. and Davis, M. (1994) “The role of NMDA receptors in learning and memory”, In: Collingridge, G.L. and Watkins, J.C., eds., The NMDA Receptor (Oxford University Press, New York). pp. 340–375.

    Google Scholar 

  • Nakagawa, T., Ozawa, T., Shige, K., Yamamoto, R., Minami, M. and Satoh, M. (2001) “Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator”, Brain Res. 419, 39–45.

    CAS  Google Scholar 

  • Narita, M., Makimura, M., Feng, Y., Hoskins, B. and Ho, I.K. (1994) “Influence of chronic morphine treatment on protein kinase C activity: comparison with butorphanol and implication for opioid tolerance”, Brain Res. 650, 175–179.

    Article  PubMed  CAS  Google Scholar 

  • Narita, M., Narita, M., Mizoguchi, H. and Tseng, L.F. (1995) “Inhibition of protein kinase C, but not of protein kinase A, blocks the development of acute antinociceptive tolerance to an intrathecally administered μ-opioid receptor agonist in the mouse”, Eur. J. Pharmacol. 280, R1-R3.

    Article  PubMed  CAS  Google Scholar 

  • Narita, M., Mizoguchi, H., Nagase, H., Suzuki, T. and Tseng, L.F. (2001) “Involvement of spinal protein kinase Cgamma in the attenuation of opioid mu-receptor-mediated G-protein activation after chronic intrathecal administration of [d-Ala2,N-MePhe4,Gly-O1(5)]enkephalin”, J. Neurosci. 21, 3715–3720.

    PubMed  CAS  Google Scholar 

  • Nedivi, E. (1999) “Molecular analysis of developmental plasticity in neocortex”, J. Neurobiol. 41, 135–147.

    Article  PubMed  CAS  Google Scholar 

  • Nestler, E.J. and Aghajanian, E.J. (1997) “Molecular and cellular basis of addiction”, Science 278, 58–63.

    Article  PubMed  CAS  Google Scholar 

  • Nibuya, M., Nestler, E. and Duman, R. (1996) “Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus”, J. Neurosci. 16, 2365–2372.

    PubMed  CAS  Google Scholar 

  • Noble, E.P. (2000) “Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review”, Eur. Psychiatry 15, 79–89.

    Article  PubMed  CAS  Google Scholar 

  • O'Brien, C.P. (1996) “Drug addiction and drug abuse”, In: Hardman, J.G., Limbird, L.E., Molinoff, P.B., Ruddon, R.W. and Gilman, A.G., eds, Goodman & Gilman's The Pharmacological Basis of Therapeutics (McGraw-Hill, New York), pp. 557–578.

    Google Scholar 

  • Orban, P.C., Chapman, P.F. and Brambilla, R. (1999) “Is the Ras-MAPK signalling pathway necessary for long-term memory formation?” Trends Neurosci. 22, 38–44.

    Article  PubMed  CAS  Google Scholar 

  • Ortiz, J., Harris, H.W., Guitart, X., Terwilliger, R.Z., Haycock, J.W. and Nestler, E.J. (1995) “Extracellular signal-regulated protein kinases (ERKs) and ERK kinase (MEK) in brain: regional distribution and regulation by chronic morphine”, J. Neurosci. 15, 1285–1297.

    PubMed  CAS  Google Scholar 

  • Ozawa, S., Kamiya, H. and Tsuzuki, K. (1998) “Glutamate receptors in the mammalian central nervous system”, Prog. Neurobiol. 54, 581–618.

    Article  PubMed  CAS  Google Scholar 

  • Parsons, C.G., Danysz, W. and Quack, G. (1999) “Memantine is a clinically well-tolerated N-methyl-d-aspartate (NMDA) receptor antagonists—a review of preclinical data”, Neuropharmacology 38, 735–767.

    Article  PubMed  CAS  Google Scholar 

  • Pataki, I. and Telegdy, G. (1998) “Further evidence that nitric oxide modifies acute and chronic morphine actions in mice”, Eur. J. Pharmacol. 357, 157–162.

    Article  PubMed  CAS  Google Scholar 

  • Peterson, D.J. and Trujillo, K.A. (2001). “The NMDA receptor antagonist memantine inhibits morphine-induced behavioral and neural plasticity,” Presented at College on Problems of Drug Dependence Annual Meeting, Scottsdale, AZ.

  • Plátenik, J., Kuramoto, N. and Yoneda, Y. (2000) “Molecular mechanisms associated with long-term consolidation of the NMDA signals”, Life Sci. 67, 335–364.

    Article  PubMed  Google Scholar 

  • Polakiewicz, R.D., Schieferl, S.M., Dorner, L.F., Kansra, V. and Comb, M.J. (1998) “A mitogen-activated protein kinase pathway is required for mu-opioid receptor desensitization”, J. Biol. Chem. 273, 12402–12406.

    Article  PubMed  CAS  Google Scholar 

  • Popik, P. and Skolnick, P. (1996) “The NMDA antagonist memantine blocks the expression and maintenance of morphine dependence”, Pharmacol Biochem. Behav. 53, 791–797.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Popik, P., Kozela, E. and Danysz, W. (2000) “Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice”, Naunyn Schmiedebergs Arch. Pharmacol. 361, 425–432.

    Article  PubMed  CAS  Google Scholar 

  • Portenoy, R. and Lesage, P. (1999) “Management of cancer pain”, Lancet 353, 1695–1700.

    Article  PubMed  CAS  Google Scholar 

  • Poser, S. and Storm, D.R. (2001) “Role of Ca4+-stimulated adenylyl cyclases in LTP and memory formation”, Int. J. Develop. Neurosci. 19, 387–394.

    Article  CAS  Google Scholar 

  • Powell, K.J., Hosokawa, A., Bell, A., Sutak, M., Milne, B., Quirion, R. and Jhamandas, K. (1999) “Comparative effects of cyclo-oxygenase and nitric oxide synthase inhibition on the development and reversal of spinal opioid tolerance”, Br. J. Pharmacol. 127, 631–644.

    Article  PubMed  CAS  Google Scholar 

  • Pozdnyakov, N., Margulis, A. and Sitaramayya, A. (1997) “Endogenous ADP-ribosylation of a G(alpha i) protein in bovine ciliary body is stimulated by nitric oxide”, Biochem. Biophys. Res. Commun. 235, 482–486.

    Article  PubMed  CAS  Google Scholar 

  • Przewlocki, R., Parsons, K.L., Sweeney, D.D., Trotter, C., Netzeband, J.G., Siggins, G.R. and Gruol, D.L. (1999) “Opioid enhancement of calcium oscillations and burst events involving NMDA receptors and L-type calcium channels in cultured hippocampal neurons”, J. Neurosci. 19, 9705–9715.

    PubMed  CAS  Google Scholar 

  • Rauhala, P., Idanpaan-Heikkila, J.J., Tuominen, R.K. and Mannisto, P.T. (1994) “N-nitro-l-arginine attenuates development of tolerance to antinociceptive but not to hormonal effects of morphine”, Eur. J. Pharmacol. 259, 57–64.

    Article  PubMed  CAS  Google Scholar 

  • Ren, K. and Dubner, R. (1999) “Central nervous system plasticity and persistent pain”, J. Orofacial Pain 13, 155–163.

    PubMed  CAS  Google Scholar 

  • Roberson, E.D., English, J.D., Adams, J.P., Selcher, J.C., Kondratick, C. and Sweatt, J.D. (1999) “The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus”, J. Neurosci. 19, 4337–4348.

    PubMed  CAS  Google Scholar 

  • Robinson, T.E. and Berridge, K.C. (1993) “The neural basis of drug craving: an incentive-sensitization theory of drug craving”, Brain Res. Rev. 18, 247–291.

    Article  PubMed  CAS  Google Scholar 

  • Rothman, R.B. (1992) “A review of the role of anti-opioid peptides in morphine tolerance and dependence”, Synapse 12, 129–138.

    Article  PubMed  CAS  Google Scholar 

  • Sadee, W. and Wang, Z. (1995) “Agonist induced constitutive receptor activation as a novel regulatory mechanism. Mu receptor regulation”, Adv. Exp. Med. Biol. 373, 85–90.

    PubMed  CAS  Google Scholar 

  • Schafe, G.E., Nader, K., Blair, H.T. and LeDoux, J.E. (2001) “Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective”, Trends Neurosci 24, 540–546.

    Article  PubMed  CAS  Google Scholar 

  • Schulteis, G. and Koob, G.F. (1996) “Reinforcement processes in opiate addiction: a homeostatic model”, Neurochem. Res. 21, 1437–1454.

    Article  PubMed  CAS  Google Scholar 

  • Schulz, S. and Hollt, V. (1998) “Opioid withdrawal activates MAP kinase in locus coeruleus neurons in morphine-dependent rats in vivo”, Eur. J. Neurosci. 10, 1196–1201.

    Article  PubMed  CAS  Google Scholar 

  • Seeburg, P.H. (1993) “The TINS/TIPS Lecture: the molecular biology of mammalian glutamate receptor channels”, Trends Neurosci. 16, 359–365.

    Article  PubMed  CAS  Google Scholar 

  • Shimoyama, N., Shimoyama, M., Inturrisi, C.E. and Elliott, K.J. (1996) “Ketamine attenuates and reverses morphine tolerance in rats”, Anesthesiology 85, 1357–1366.

    Article  PubMed  CAS  Google Scholar 

  • Silva, A.J., Kogan, J.H. Frankland, P.W. and Kida, S. (1998) “CREB and memory”, Annu. Rev. Neurosci. 21, 127–148.

    Article  PubMed  CAS  Google Scholar 

  • Smart, D. and Lambert, D.G. (1996) “The stimulatory effects of opioids and their possible role in the development of tolerance”, Trends Pharmacol. Sci. 17, 264–269.

    Article  PubMed  CAS  Google Scholar 

  • Smart, D., Hirst, R.A., Hirota, K., Grandy, D.K. and Lambert, D.G. (1997) “The effects of recominant rat μ-opioid receptor activation in CHO cell on phospholipase C, [Ca2+]i and adenylyl cyclase”, Br. J. Pharmacol. 120, 1165–1171.

    Article  PubMed  CAS  Google Scholar 

  • Smith, F.L., Lohmann, A.B. and Dewey, W.L. (1999) “Involvement of phospholipid signal transduction in morphine tolerance in mice”, Br. J. Pharmacol. 128, 220–226.

    Article  PubMed  CAS  Google Scholar 

  • Soderling, T.R. and Derkach, V.A. (2000) “Postsynaptic protein phosphorylation and LTP”, Trends Neurosci. 23, 75–80.

    Article  PubMed  CAS  Google Scholar 

  • Squire, L.R. and Kandel, F.R. (2000) Memory: From Mind to Molecules (Scientific American Library, New York).

    Google Scholar 

  • Stephens, D.N. (1995) “A glutamatergic hypothesis of drug dependence: extrapolations from benzodiazepine receptor ligands”, Behav. Pharmacol. 6, 425–446.

    PubMed  CAS  Google Scholar 

  • Stewart, J. and Badiani, A. (1993) “Tolerance and sensitization to the behavioral effects of drugs”, Behav. Pharmacol. 4, 289–312.

    PubMed  CAS  Google Scholar 

  • Su, M.-T., Lin, W.-B., Lue, W.-M., Cheng, C.-Y and Tao, P.-L. (1998) “Blockade of the development of morphine tolerance by U-50,488, and AVP antagonist or MK-801 in the rat hippocampal slice”, Br. J. Pharmacol. 123, 625–630.

    Article  PubMed  CAS  Google Scholar 

  • Swadley-Lewellen, R.M. and Trujillo, K.A. (1998) “Are NMDA receptors involved in tolerance and sensitization to the locomotor effects of morphine?”, Soc. Neurosci. Abstr. 24, 1968.

    Google Scholar 

  • Szeto, C.Y., Tang, N.L., Lee, D.T. and Stadlin, A. (2001) “Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts”, Neuroreport 12, 1103–1106.

    Article  PubMed  CAS  Google Scholar 

  • Takemori, A.E. (1974) “Biochemistry of drug dependence”, Annu. Rev. Biochem. 43, 15–33.

    Article  PubMed  CAS  Google Scholar 

  • Tiffany, S.T. and Maude-Griffith, P.M. (1988) “Tolerance to morphine in the rat: associative and non-associative effects”, Behav. Neurosci. 102, 534–543.

    Article  PubMed  CAS  Google Scholar 

  • Tiseo, P.J. and Inturrisi, C.E. (1993) “Attenuation and reversal of morphine tolerance by the competitive N-methyl-d-aspartate receptor antagonist LY274614”, J. Pharmacol. Exp. Ther. 264, 1090–1096.

    PubMed  CAS  Google Scholar 

  • Tiseo, P.J., Cheng, J., Pasternak, G.W. and Inturrisi, C.E. (1994) “Modulation of morphine tolerance by the competitive N-methyl-d-aspartate receptor antagonist LY274614: assessment of opioid receptor changes”, J. Pharmacol. Exp. Ther. 268, 195–201.

    PubMed  CAS  Google Scholar 

  • Trapaidze, N., Gomes, I., Cvejic, S., Bansinath, M. and Devi, L.A. (2000) “Opioid receptor endocytosis and activation of MAP kinase pathway”, Mol. Brain Res. 76, 220–228.

    Article  PubMed  CAS  Google Scholar 

  • Trujillo, K.A. (1999) “Cellular and molecular mechanisms of opioid tolerance and dependence: progress and pitfalls”, Pain Forum 8, 29–33.

    Google Scholar 

  • Trujillo, K.A. (2000) “Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical findings”, Psychopharmacology 151, 121–141.

    Article  PubMed  CAS  Google Scholar 

  • Trujillo, K.A. (2002) “The role of NMDA receptors in opiate-induced neural and behavioral plasticity: a review of preclinical studies, a cellular model, and clinical implications”, In: Herman, B.H., Frankenheim, J., Litten, R., Sheridan, P.H., Weight, F.F. and Zukin, S.R., eds, Glutamate and Addiction (Humana, Totowa NJ), In press.

    Google Scholar 

  • Trujillo, K.A. and Akil, H. (1990) “Behavioral interactions between morphine and MK-801: analgesia, tolerance, dependence and lethality”, Soc. Neurosci. Abstr. 16, 211.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Trujillo, K.A. and Akil, H. (1991b) “Opiate tolerance and dependence: Recent findings and synthesis”, New Biol. 3, 915–923.

    PubMed  CAS  Google Scholar 

  • Trujillo, K.A. and Akil, H. (1995) “Excitatory amino acids and drugs of abuse: Arole for N-methyl-d-aspartate receptors in drug tolerance, sensitization and physical dependence”, Drug. Alcohol Depend. 38, 139–154.

    Article  PubMed  CAS  Google Scholar 

  • Trujillo, K.A. and Watorski, K. (1999) “Does MK-801 affect the expression of opiate tolerance, sensitization or physical dependence”, Soc. Neurosci. Abstr. 25, 2076.

    Google Scholar 

  • Trujillo, K.A., Bronstein, D.M. and Akil, H. (1991) “Inhibition of morphine tolerance and dependence by MK-801: Behavioral and neurochemical studies”, Soc. Neurosci. Abstr. 17, 331.

    Google Scholar 

  • Trujillo, K.A., Warmoth, K.P., Peterson, D.J., Albertson, D.N. and Swadley-Lewellen, R.M. (2000). “NMDA receptor blockade mimics tolerance to the locomotor effects of morphine”, Presented at International Narcotics Research Conference, Seattle, WA.

  • Trujillo, K.A., Warmoth, K.P., Peterson, D.J., Albertson, D.N., Watorski, K. and Swadley-Lewellen, R.M. (2001) “NMDA receptor antagonists inhibit the development of tolerance and sensitization to the locomotor effects of opiates”, Soc. Neurosci. Abstr. 27, #224211.

    Google Scholar 

  • Tzschentke, T.M. and Schmidt, W.J. (1996) “Procedural examination of behavioral sensitisation to morphine: lack of blockade by MK-801, occurrence of sensitised sniffing, and evidence for cross-sensitisation between morphine and MK-801”, Behav. Pharmacol. 7, 169–184.

    PubMed  CAS  Google Scholar 

  • Ueda, H., Miyamae, T., Fukushima, N., Takeshima, H., Fukuda, K., et al., (1995) “Opioid μ-and k-receptor mediate phospholipase C activation through Gi1 in Xenopus oocytes”, Mol. Brain. Res. 32, 166–170.

    Article  PubMed  CAS  Google Scholar 

  • Ueda, H., Inoue, M. and Matsumoto, T. (2001) “Protein kinase C-mediated inhibition of mu-opioid receptor internalization and its involvement in the development of acute tolerance to peripheral mu-agonist analgesia”, J. Neurosci. 21, 2967–2973.

    PubMed  CAS  Google Scholar 

  • Uhl, G.R., Elmer, G.I., LaBuda, M.C. and Pickens, R.W. (1995) “Genetic influences in drug abuse”, In: Bloom, F.E. and Kupfer, D.J., eds, Psychopharmacology: The Fourth Generation of Progress (Raven Press, New York), pp. 1793–1806.

    Google Scholar 

  • Uhl, G.R., Sora, I. and Wang, Z. (1999) “The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses”, Proc. Natl Acad. Sci. USA 96, 7752–7755.

    Article  PubMed  CAS  Google Scholar 

  • Vanderschuren, L.J., Schoffelmeer, A.N. and De Vries, T.J. (1997) “Does dizocilpine (MK-801) inhibit the development of morphine-induced behavioral sensitization in rats?” Life Sci., 61

  • Vasko, M.R. and Domino, E.F. (1978) “Tolerance development to the biphasic effects of morphine on locomotor activity and brain acetylcholine in the rat”, J. Pharmacol. Exp. Ther. 207, 848–858.

    PubMed  CAS  Google Scholar 

  • Ventayol, P., Busquets, X. and Garcia-Sevilla, J.A. (1997) “Modulation of immunoreactive protein kinase C-alpha and beta isoforms and G proteins by acute and chronic treatments with morphine and other opiate drugs in rat brain”, Naunyn Schmiedebergs Arch. Pharmacol. 355, 491–500.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L. and Gintzler, A.R. (1995) “Morphine tolerance and physical dependence: reversal of opioid inhibition to enhancement of cyclic AMP formation”, J. Neurochem. 64, 1102–1106.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L. and Gintzler, A.R. (1997) “Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure”, J. Neurochem. 68, 248–254.

    PubMed  CAS  Google Scholar 

  • Wang, H. and Pickel, V.M. (2000) “Presence of NMDA-type glutamate receptors in cingulate corticostriatal terminals and their postsynaptic targets”, Synapse 35, 210–300.

    Article  Google Scholar 

  • Wang, Z., Bilsky, E.J., Porreca, F. and Sadee, W. (1994) “Constituitive μ opioid receptor activation as a regulatory mechanism underlying narcotic tolerance and dependence”, Life Sci. 54, PL339-PL350.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L., Medina, V.M., Rivera, M. and Gintzler, A.R. (1996a) “Relevance of phosphorylation state to opioid responsiveness in opiate naive and tolerant/dependent tissue”, Brain Res. 723, 61–69.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Z., Arden, J. and Sadee, W. (1996b) “Basal phosphorylation of mu opioid receptor is agonist modulated and Ca2+-dependent”, FEBS Lett. 387, 53–57.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H., Gracy, K.N. and Pickel, V.M. (1999) “Mu-opioid and NMDA-type glutamate receptors are often colocalized in spiny neurons within patches of the caudate-putamen nucleus”, J. Comp. Neurol. 412, 132–146.

    Article  PubMed  CAS  Google Scholar 

  • Wang, D., Tolbert, L.M., Carlson, K.W. and Sadee, W. (2000) “Nuclear Ca2+/calmodulin translocation activated by mu-opioid (OP3) receptor”, J. Neurochem. 74, 1418–1425.

    Article  PubMed  CAS  Google Scholar 

  • Wang, D., Raehal, K.M., Bilsky, E.J. and Sadee, W. (2001) “Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence”, J. Neurochem. 77, 1590–1600.

    Article  PubMed  CAS  Google Scholar 

  • Whistler, J.L. and von Zastrow, M. (1999) “Dissociation of functional roles of dynamin in receptor-mediated endocytosis and mitogenic signal transduction”, J. Biol. Chem. 274, 24575–24578.

    Article  PubMed  CAS  Google Scholar 

  • Whistler, J.L., Chuang, H.H., Chu, P., Jan, L.Y. and von Zastrow, M. (1999) “Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction”, Neuron 23, 737–746.

    Article  PubMed  CAS  Google Scholar 

  • Williams, J.T., Christie, M.J. and Manzoni, O. (2001) “Cellular and synaptic adaptations mediating opioid dependence”, Physiol. Rev. 81, 299–343.

    PubMed  CAS  Google Scholar 

  • Wolf, M.E. (1998) “The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants”, Prog. Neurobiol. 54, 679–720.

    Article  PubMed  CAS  Google Scholar 

  • Wolf, M.E. and Jeziorski, M. (1993) “Coadministration of MK-801 with amphetamine, cocaine or morphine prevents rather than transiently masks the development of behavioral sensitization”, Brain Res. 613, 291–294.

    Article  PubMed  CAS  Google Scholar 

  • Wong, C.-S., Cherng, C.-H., Luk, H.-N., Ho, S.-T. and Tung, C.-S. (1996) “Effects of NMDA receptor antagonists on inhibition of morphine tolerance in rats: binding at μ-opioid receptors”, Eur. J. Pharmacol. 297, 27–33.

    Article  PubMed  CAS  Google Scholar 

  • Wong, A.H., Buckle, C.E. and Van Tol, H.H. (2000) “Polymorphisms in dopamine receptors: what do they tell us?”, Eur. J. Pharmacol. 410, 183–203.

    Article  PubMed  CAS  Google Scholar 

  • Xie, W., Samoriski, G.M., McLaughlin, J.P., Romoser, V.A., Smrcka, A., Hinkle, P.M., Bidlack, J.M., Gross, R.A., Jiang, H. and Wu, D. (1999) “Genetic alterations of phospholipase C β3 expression modulates behavioral and cellular responses to μ opioids”, Proc. Natl Acad. Sci. USA 96, 10385–10390.

    Article  PubMed  CAS  Google Scholar 

  • Xu, J.Y., Hill, K.P. and Bidlack, J.M. (1998) “The nitric oxide/cyclic GMP system at the supraspinal site is involved in the development of acute morphine antinociceptive tolerance”, J. Pharmacol. Exp. Ther. 284, 196–201.

    PubMed  CAS  Google Scholar 

  • Yamakura, T. and Shimoji, K. (1999) “Subunit- and site-specific pharmacology of the NMDA receptor channel”, Prog. Neurobiol. 59, 279–298.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, L., Yu, Y., Mackin, S., Weight, F.F., Uhl, G.R. and Wang, J.B. (1996) “Differential μ opiate receptor phosphorylation and desensitization induced by agonists and phorbol esters”, J. Biol. Chem. 271, 11449–11454.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, G.M. and Bhargava, H.N. (1996) “Nitric oxide synthase inhibition attenuates tolerance to morphine but not to [d-Ala2, Glu4] deltorphin II, a delta 2-opioid receptor agonist in mice”, Peptides 17, 619–623.

    Article  PubMed  Google Scholar 

  • Zheng, X., Zhang, L., Wang, A.P., Bennett, M.V. and Zukin, R.S. (1999) “Protein kinase C potentiation of N-methyl-d-aspartate receptor activity is not mediated by phosphorylation of N-methyl-d-aspartate receptor subunits”, Proc. Natl Acad. Sci. USA 96, 15262–15267.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, H. and Ho, I.K. (1998) “NMDA-R1 antisense oligonucleotide attenuates withdrawal signs from morphine”, Eur. J. Pharmacol. 352, 151–156.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, California State University San Marcos, 92096-0001, San Marcos, CA, USA

    Keith A. Trujillo

Authors
  1. Keith A. Trujillo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith A. Trujillo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trujillo, K.A. The neurobiology of opiate tolerance, dependence and sensitization: Mechanisms of NMDA receptor-dependent synaptic plasticity. neurotox res 4, 373–391 (2002). https://doi.org/10.1080/10298420290023954

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/10298420290023954

Keywords

Search

Navigation