Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.

ABSTRACT: Opioid use disorder (OUD) is associated with a withdrawal-induced negative affective state, which contributes to uncontrolled use via negative reinforcement. The orexin (hypocretin) system is implicated in physical opioid withdrawal. We sought to test whether the orexin system is involved in negative affect during withdrawal from chronic prescription opioid exposure. Rats received non-contingent saline or oxycodone over 21d and were assessed for behaviors indicative of negative affect. We tested whether chronic oxycodone was associated with changes in orexin cell number or activity. We used chemogenetics in transgenic rats to modulate the activity of orexin neurons to determine their functional role in development of negative affect. Chronic oxycodone induced a negative affective state dur

SUBMITTER: Newman KA 

PROVIDER: S-EPMC12633195 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature