Department of Psychobiology, Faculty of Psychology, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
Department of Physiology, School of Medicine, Universitat de Valencia, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain.
Int J Mol Sci. 2024 Aug 19;25(16):9002. doi: 10.3390/ijms25169002.
Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1β, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse.
油酰乙醇酰胺（OEA）是一种具有抗炎活性的脂质，可调节多种与奖励相关的行为。先前的研究表明，OEA 治疗可减少酒精自我给药（SA），同时抑制酒精诱导的炎症信号。然而，OEA 实现这些效果的具体机制尚未得到广泛探索。在这里，我们测试了 OEA 在酒精 SA、消退或之前的线索诱导复吸期间治疗的效果。此外，我们测量了与酒精消耗相关的受体（Drd1、Drd2、Cnr1、Oprm）以及免疫相关蛋白（Il-6、Il-1β、Tlr4）和脑源性神经营养因子（Bdnf）在纹状体和海马中的基因表达变化。我们的结果证实，当系统给予时，OEA 给药可减少酒精 SA，并减弱线索诱导的复吸。有趣的是，我们还观察到 OEA 治疗减少了酒精寻求消退所需的疗程数。生化分析表明，OEA 诱导了纹状体和海马中的多巴胺和大麻素受体的基因表达变化。此外，OEA 治疗调节了长期的免疫反应并增加了 Bdnf 的表达。这些结果表明，提高 OEA 水平可能是减少酒精 SA 和预防复发的有效策略。
