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Papers of the Week

Papers: 10 Apr 2021 - 16 Apr 2021

Pharmacology/Drug Development

2021 Apr

Sci Adv



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


Pantazis CB, Gonzalez LA, Tunstall BJ, Carmack SA, Koob GF, Vendruscolo LF
Sci Adv. 2021 Apr; 7(15).
PMID: 33827822.


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.