Advances in the characterization of negative affect caused by acute and protracted opioid withdrawal using animal models

Opioid use disorder (OUD) is a chronic brain disease which originates from long-term neuroadaptations that develop after repeated opioid consumption and withdrawal episodes. These neuroadaptations lead among other things to the development of a negative affect, which includes loss of motivation for natural rewards, higher anxiety, social deficits, heightened stress reactivity, an inability to identify and describe emotions, physical and/or emotional pain, malaise, dysphoria, sleep disorders and chronic irritability. The urge for relief from this negative affect is one of major causes of relapse, and thus represents a critical challenge for treatment and relapse prevention. Animal models of negative affect induced by opioid withdrawal have recapitulated the development of a negative emotional state with signs such as anhedonia, increased anxiety responses, increased despair-like behaviour and deficits in social interaction. This research has been critical to determine neurocircuitry adaptations during chronic opioid administration or upon withdrawal. In this review, we summarize the recent literature of rodent models of (i) acute withdrawal, (ii) protracted abstinence from passive administration of opioids, (iii) withdrawal or protracted abstinence from opioid self-administration. Finally, we describe neurocircuitry involved in acute withdrawal and protracted abstinence.This article is part of the Special Issue on Opioid-induced changes in addiction and pain circuits.

Automated summary

Opioid use disorder is a chronic brain disease caused by long-term neuroadaptations resulting from repeated opioid consumption and withdrawal. These neuroadaptations lead to negative affect and various symptoms, such as loss of motivation, anxiety, social deficits, heightened stress reactivity, emotional and physical pain, dysphoria, sleep disorders, and chronic irritability. Understanding the neurocircuitry involved in withdrawal and abstinence is crucial for treatment and relapse prevention.