Alghamdi Badrah S, Alshehri Fahad S
Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Behav Neurosci. 2021 Oct 14;15:762297. doi: 10.3389/fnbeh.2021.762297. eCollection 2021.
Opioid addiction remains a widespread issue despite continuous attempts by the FDA to help maintain abstinence. Melatonin is a neurohormone considered to be involved only in the neuroendocrine and reproductive systems; however, recent reports have demonstrated its potential to attenuate drug addiction and dependence. Cumulative studies have suggested that melatonin can attenuate the rewarding effects of several drugs of abuse, including opioids. This study aimed to investigate the effect of melatonin (50 mg/kg) on morphine (5 mg/kg) to produce place preference. We also investigated the effect of melatonin and morphine on the expression of GLT-1, BDNF, NF-κB, and CREB within the nucleus accumbens. Male Wistar rats were divided into control, morphine, melatonin, and the morphine + melatonin groups. The study involved a two-phase habituation phase from day 1 to day 3 and an acquisition phase from day 5 to day 14. The conditioned place preference (CPP) score, distance traveled, resting time, ambulatory count, and total activity count were measured for all animals. Rats that received morphine showed a significant increase in CPP score compared to those in the control group. Morphine treatment reduced the mRNA expression of GLT-1, BDNF, and CREB and increased that of NF-κB. However, melatonin treatment administered 30 min before morphine treatment attenuated morphine place preference and reversed GLT-1, BDNF, NF-κB, and CREB expression levels. In conclusion, the study results indicate, for the first time, the new potential targets of melatonin in modulating morphine-induced CPP.
尽管美国食品药品监督管理局（FDA）不断努力帮助维持戒毒状态，但阿片类药物成瘾仍然是一个普遍存在的问题。褪黑素是一种神经激素，以往认为仅参与神经内分泌和生殖系统；然而，最近的报告表明它有减轻药物成瘾和依赖的潜力。累积研究表明，褪黑素可以减轻包括阿片类药物在内的几种滥用药物的奖赏效应。本研究旨在调查褪黑素（50毫克/千克）对吗啡（5毫克/千克）产生位置偏爱效应的影响。我们还研究了褪黑素和吗啡对伏隔核内谷氨酸转运体-1（GLT-1）、脑源性神经营养因子（BDNF）、核因子κB（NF-κB）和环磷腺苷效应元件结合蛋白（CREB）表达的影响。雄性Wistar大鼠被分为对照组、吗啡组、褪黑素组和吗啡+褪黑素组。该研究包括从第1天到第3天的两阶段习惯化阶段和从第5天到第14天的获得阶段。测量了所有动物的条件性位置偏爱（CPP）得分、行进距离、休息时间、活动计数和总活动计数。与对照组相比，接受吗啡的大鼠CPP得分显著增加。吗啡治疗降低了GLT-1、BDNF和CREB的mRNA表达，并增加了NF-κB的表达。然而，在吗啡治疗前30分钟给予褪黑素治疗减弱了吗啡位置偏爱，并逆转了GLT-1、BDNF、NF-κB和CREB的表达水平。总之，研究结果首次表明了褪黑素在调节吗啡诱导的CPP中的新潜在靶点。
