VTA μ-opioidergic neurons facilitate low sociability in protracted opioid withdrawal.

Abstract

The compelling urge for relief from negative affective states during long-term opioid withdrawal presents a crucial challenge for maintaining abstinence. The ventral tegmental area (VTA) and its mu-opioid receptor-expressing (VTA MOR ) neurons represent a critical target of opioidergic action that underlie dependence and withdrawal. Chronic activation of VTA MOR neurons during opioid exposure induces maladaptations within these neurons and their structurally connected circuitries, which alter reward processing and contribute to negative affect. Using an oral morphine drinking paradigm to induce dependence, we demonstrate that withdrawal engages VTA MOR neurons and identify this neuronal population as key mediators of opioid withdrawal-induced social deficits. These findings hold promise to inform development of targeted therapies aimed at alleviating negative affective states associated with protracted opioid withdrawal.