Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
Am J Drug Alcohol Abuse. 2021 Jan 2;47(1):43-51. doi: 10.1080/00952990.2020.1813296. Epub 2020 Oct 2.
Opioids are effective analgesics in the management of chronic pain. However, their clinical use is hindered by adverse side effects such as addiction and analgesic tolerance. Naringenin is a common polyphenolic constituent of the citrus fruits and is one of the most commonly consumed flavonoids within our regular diet. However, its influences on opioid tolerance and addiction have not yet been clarified.
To examine the effect of different doses of naringenin on analgesic tolerance, conditioned place preference and neuroinflammation in morphine-exposed rats.
Analgesic tolerance was induced by the injection of 10 mg/kg morphine twice daily for 8 days in 70 male Wistar rats. To evaluate the effect of naringenin on the development of morphine tolerance, different doses (10, 25 and 50 mg/kg i.p.) were injected 15 min before morphine. The tail-flick test was used to assess nociceptive threshold. Conditioned place preference test was used to evaluate morphine-seeking behaviors. The lumbar spinal cord was assayed to determine glial fibrillary acidic protein (GFAP) and cyclooxygenase-2 (COX-2) levels by Western blotting.
The data showed that naringenin could significantly prevent morphine tolerance ( < .001) and conditioned place preference. In addition, chronic morphine-induced GFAP and COX-2 overexpression was significantly reversed by 50 mg/kg naringenin ( < .05 and < .01, respectively).
Our results suggest that naringenin may have a potential anti-tolerant/anti-addiction property against chronic morphine misuse and that this preventive effect is associated with its anti-neuroinflammatory effects.
阿片类药物在慢性疼痛管理中是有效的镇痛药。然而，它们的临床应用受到不良反应的阻碍，如成瘾和镇痛耐受。柚皮素是柑橘类水果中常见的多酚成分，也是我们日常饮食中最常消费的类黄酮之一。然而，它对阿片类药物耐受和成瘾的影响尚未阐明。
研究不同剂量柚皮素对吗啡暴露大鼠的镇痛耐受、条件性位置偏爱和神经炎症的影响。
通过每天两次注射 10mg/kg 吗啡，共 8 天，在 70 只雄性 Wistar 大鼠中诱导镇痛耐受。为了评估柚皮素对吗啡耐受发展的影响，在注射吗啡前 15 分钟注射不同剂量（10、25 和 50mg/kg，ip）。尾闪烁试验用于评估痛觉阈值。条件性位置偏爱试验用于评估吗啡寻求行为。通过 Western 印迹法测定腰椎脊髓中的胶质纤维酸性蛋白（GFAP）和环氧化酶-2（COX-2）水平。
数据表明，柚皮素能显著预防吗啡耐受（<0.001）和条件性位置偏爱。此外，慢性吗啡诱导的 GFAP 和 COX-2 过度表达被 50mg/kg 柚皮素显著逆转（分别为 <0.05 和 <0.01）。
我们的结果表明，柚皮素可能对慢性吗啡滥用具有潜在的抗耐受/抗成瘾特性，这种预防作用与其抗神经炎症作用有关。
