Melatonin is a neurohormone synthesized by the pineal gland to regulate the circadian rhythms and has proven to be effective in treating drug addiction and dependence. However, the effects of melatonin to modulate the drug-seeking behavior of fentanyl and its underlying molecular mechanism is elusive. This study was designed to investigate the effects of melatonin on fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice. The accompanying changes in the expression of Brain and Muscle Arnt-Like (BMAL1), tyrosine hydroxylase (TH), and monoamine oxidase A (MAO-A) in relevant brain regions including the suprachiasmatic nucleus (SCN), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus (Hip) were investigated by western blot assays to dissect the mechanism by which melatonin modulates fentanyl - induced behavioral sensitization and circadian rhythm disorders. The present study suggest that fentanyl (0.05, 0.1 and 0.2 mg/kg) could induce behavioral sensitization and melatonin (30.0 mg/kg) could attenuate the behavioral sensitization and circadian rhythm disorders in mice. Fentanyl treatment reduced the expression of BMAL1 and MAO-A and increased that of TH in relevant brain regions. Furthermore, melatonin treatment could reverse the expression levels of BMAL1, MAO-A, and TH. In conclusion, our study demonstrate for the first time that melatonin has therapeutic potential for fentanyl addiction.

中文翻译：

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褪黑激素减轻芬太尼引起的小鼠行为过敏和昼夜节律紊乱

褪黑激素是一种由松果体合成的神经激素，可调节昼夜节律，已被证明可有效治疗药物成瘾和依赖性。然而，褪黑激素调节芬太尼寻药行为的作用及其潜在的分子机制尚不清楚。本研究旨在研究褪黑激素对芬太尼诱导的小鼠行为过敏和昼夜节律紊乱的影响。相关脑区域（包括视交叉上核（SCN）、伏核（NAc）、通过蛋白质印迹分析对前额皮质 (PFC) 和海马体 (Hip) 进行研究，以剖析褪黑激素调节芬太尼诱导的行为敏化和昼夜节律紊乱的机制。目前的研究表明，芬太尼（0.05、0.1和0.2 mg/kg）可以诱导小鼠行为过敏，而褪黑激素（30.0 mg/kg）可以减轻小鼠的行为过敏和昼夜节律紊乱。芬太尼治疗降低了相关脑区 BMAL1 和 MAO-A 的表达，并增加了 TH 的表达。此外，褪黑激素治疗可以逆转 BMAL1、MAO-A 和 TH 的表达水平。总之，我们的研究首次证明褪黑激素具有治疗芬太尼成瘾的潜力。