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Cues conditioned to withdrawal and negative reinforcement: Neglected but key motivational elements driving opioid addiction.

Abstract
Opioid use disorder (OUD) is a debilitating disorder that affects millions of people. Neutral cues can acquire motivational properties when paired with the positive emotional effects of drug intoxication to stimulate relapse. However, much less research has been devoted to cues that become conditioned to the aversive effects of opioid withdrawal. We argue that environmental stimuli promote motivation for opioids when cues are paired with withdrawal (conditioned withdrawal) and generate opioid consumption to terminate conditioned withdrawal (conditioned negative reinforcement). We review evidence that cues associated with pain drive opioid consumption, as patients with chronic pain may misuse opioids to escape physical and emotional pain. We highlight sex differences in withdrawal-induced stress reactivity and withdrawal cue processing and discuss neurocircuitry that may underlie withdrawal cue processing in dependent individuals. These studies highlight the importance of studying cues associated with withdrawal in dependent individuals and point to areas for exploration in OUD research.
AuthorsCaroline B Pantazis, Luis A Gonzalez, Brendan J Tunstall, Stephanie A Carmack, George F Koob, Leandro F Vendruscolo
JournalScience advances (Sci Adv) Vol. 7 Issue 15 (04 2021) ISSN: 2375-2548 [Electronic] United States
PMID33827822 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
CopyrightCopyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Chemical References
  • Analgesics, Opioid
Topics
  • Analgesics, Opioid
  • Chronic Pain (psychology)
  • Cues
  • Female
  • Humans
  • Male
  • Motivation
  • Opioid-Related Disorders (psychology)
  • Reinforcement, Psychology
  • Substance Withdrawal Syndrome

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