Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.

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.

journal_name

Trends Pharmacol Sci

authors

Cahill CM,Walwyn W,Taylor AMW,Pradhan AAA,Evans CJ

doi

10.1016/j.tips.2016.08.002

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

963-976

issue

11

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(16)30106-7

journal_volume

37

pub_type

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