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 Scijournal_title
Trends in pharmacological sciencesauthors
Cahill CM,Walwyn W,Taylor AMW,Pradhan AAA,Evans CJdoi
10.1016/j.tips.2016.08.002subject
Has Abstractpub_date
2016-11-01 00:00:00pages
963-976issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(16)30106-7journal_volume
37pub_type
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