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Trends Pharmacol Sci. 2016 Nov;37(11):963-976. doi: 10.1016/j.tips.2016.08.002. Epub 2016 Sep 23.

Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.

Author information

1
Department of Anesthesiology and Perioperative Care, University of California, Irvine, 837 Health Sciences Road, Irvine, CA 92697, USA.
2
Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
3
Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA.
4
Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, CA 90095, USA. Electronic address: cevans@ucla.edu.

Abstract

Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs.

KEYWORDS:

arrestin; bias signaling; dopamine; microglia; opponent processes; reward; μ opioid receptor

PMID:
27670390
PMCID:
PMC5240843
DOI:
10.1016/j.tips.2016.08.002
[Indexed for MEDLINE]
Free PMC Article

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