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Individual differences in orexin‐I receptor modulation of motivation for the opioid remifentanil
Author(s) -
PorterStransky Kirsten A.,
Bentzley Brandon S.,
AstonJones Gary
Publication year - 2017
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12323
Subject(s) - remifentanil , opioid , orexin , psychology , price elasticity of demand , behavioral economics , antagonism , anesthesia , medicine , receptor , economics , microeconomics , neuropeptide , propofol
Orexin‐1 receptors (Ox1Rs) have been implicated in the motivation for drugs of abuse. Here, we utilized a within‐session behavioral‐economics threshold procedure to screen for individual differences in economic demand for the ultra‐short‐acting opioid remifentanil and to test whether antagonism of Ox1Rs reduces remifentanil demand. The behavioral‐economics procedure revealed robust individual differences in free consumption of remifentanil (Q 0 parameter; hedonic set point). Rats with low baseline Q 0 (low takers) displayed high demand elasticity (α parameter; reduced responding as drug price increased indicating low motivation for drug), whereas subjects with a higher Q 0 (high takers) exhibit low demand elasticity (low α) by continuing to self‐administer remifentanil despite increased cost (reflecting higher motivation for drug). In a punished responding paradigm utilizing footshock, subjects that were classified as high takers at baseline withstood twice as much shock as low takers to continue self‐administering remifentanil. Interestingly, Ox1R antagonism with SB‐334867 reduced Q 0 and increased α in low takers but not in high takers. Similarly, the Ox1R antagonist attenuated cue‐induced, but not drug‐induced, reinstatement of remifentanil seeking in low takers but had no significant effect on reinstatement of drug seeking in high takers. Together, these data reveal a novel role of orexins in demand for remifentanil: Ox1Rs modulate demand in low takers but not in individuals that exhibit addictive‐like behaviors (high takers). Finally, the behavioral assays in this study can serve as a novel laboratory model for studying individual differences in opioid use disorders.