TY - JOUR
T1 - Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation
AU - Cahill, Catherine M.
AU - Walwyn, Wendy
AU - Taylor, Anna M.W.
AU - Pradhan, Amynah A.A.
AU - Evans, Christopher J.
N1 - Publisher Copyright:
© 2016
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - arrestin
KW - bias signaling
KW - dopamine
KW - microglia
KW - opponent processes
KW - reward
KW - μ opioid receptor
UR - http://www.scopus.com/inward/record.url?scp=84992337614&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2016.08.002
DO - 10.1016/j.tips.2016.08.002
M3 - Review article
C2 - 27670390
AN - SCOPUS:84992337614
SN - 0165-6147
VL - 37
SP - 963
EP - 976
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 11
ER -