IMR Press / FBL / Volume 14 / Issue 14 / DOI: 10.2741/3596

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Mechanisms underlying morphine analgesic tolerance and dependence
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1 Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

Academic Editor: Yingxian Pan

Front. Biosci. (Landmark Ed) 2009, 14(14), 5260–5272;
Published: 1 June 2009
(This article belongs to the Special Issue regulation and function of opioid receptor genes)

The mechanisms underlying opioid tolerance are not fully understood, but appear to be comprised of two types of plasticity or counter-adaptation, at the cellular level and through neuronal circuits. Current studies mostly emphasize the cellular adaptation mechanisms, which include altered gene expression and receptor desensitization due to phosphorylation and endocytosis. However, the mechanisms underlying opioid tolerance and dependence are not always explained by cellular adaptation mechanisms alone. This review focuses on the plasticity in neuronal circuits achieved through an enhancement of synaptic activities between glutamate and NMDA receptor due to up-regulation of receptor and racemase to produce D-serine, an allosteric NMDA receptor agonist, and down-regulation of glutamate transporter, all which contribute to the counterbalance of opioid actions or anti-opioid mechanisms underlying opioid tolerance. This anti-opioid system is supposed to be also augmented by altered expression of key molecules regulating through neuron-glial networks. This review also introduces a new approach using in vivo electroporation to identify the brain loci responsible for morphine tolerance and dependence.

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