Wabreha Ammanuel Y, McCoy Michael T, Cadet Jean Lud, Daiwile Atul P
Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Int J Mol Sci. 2025 Jul 30;26(15):7356. doi: 10.3390/ijms26157356.
The diagnosis of opioid use disorder (OUD) is prevalent due to increased prescribing of opioids. Long-term oxycodone self-administration can lead to addiction-like behavioral responses in rats. Herein, we sought to identify molecular pathways consequent to long-term exposure to oxycodone self-administration. Towards that end, we used male Sprague Dawley rats that self-administered oxycodone for 20 days according to short-(ShA, 3 h) and long-access (LgA, 9 h) paradigms. LgA rats escalated their oxycodone intake and developed into 2 phenotypes, labeled Long-access High (LgA-H) and Long-access Low (LgA-L) rats, based on their escalation. RNA sequencing analysis revealed the LgA-H has significantly different DEGs in comparison to other groups. DAVID analysis revealed the participation of LgA-H DEGs in potassium transport. RT-PCR analysis of striatal samples validated the increased levels of potassium channels. Since these increases correlated with oxycodone intake, we believe potassium channels are potential targets for the treatment of oxycodone use disorder.
由于阿片类药物处方量增加，阿片类药物使用障碍（OUD）的诊断很普遍。长期自我给药羟考酮会导致大鼠出现类似成瘾的行为反应。在此，我们试图确定长期暴露于自我给药羟考酮后产生的分子途径。为此，我们使用雄性Sprague Dawley大鼠，根据短（ShA，3小时）和长给药时间（LgA，9小时）模式，让它们自我给药羟考酮20天。LgA组大鼠的羟考酮摄入量增加，并根据其增加情况发展为两种表型，分别标记为长给药时间高摄入量（LgA-H）和长给药时间低摄入量（LgA-L）大鼠。RNA测序分析显示，与其他组相比，LgA-H组有显著不同的差异表达基因（DEG）。DAVID分析显示LgA-H组的DEG参与钾转运。对纹状体样本的RT-PCR分析证实了钾通道水平的增加。由于这些增加与羟考酮摄入量相关，我们认为钾通道是治疗羟考酮使用障碍的潜在靶点。
