Cellular and Molecular Research Center, Department of Neuroscience, Iran University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Alcohol. 2024 Feb;114:9-24. doi: 10.1016/j.alcohol.2023.08.004. Epub 2023 Aug 18.
Evidence has suggested that addiction and memory systems are related, but the signaling cascades underlying this interaction have not been completelyealed yet. The importance of calcium-calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) in the memory processes and also in drug addiction has been previously established. In this present investigation, we examined the effects of repeated morphine pretreatment on impairment of spatial learning and memory acquisition induced by systemic ethanol administration in adult male rats. Also, we assessed how these drug exposures influence the expression level of CaMKII and BDNF in the hippocampus and amygdala. Animals were trained by a single training session of 8 trials, and a probe test containing a 60-s free-swim without a platform was administered 24 h later. Before training trials, rats were treated with a once-daily subcutaneous morphine injection for 3 days followed by a 5-day washout period. The results showed that pre-training ethanol (1 g/kg) impaired spatial learning and memory acquisition and down-regulated the mRNA expression of CaMKII and BDNF. The amnesic effect of ethanol was suppressed in morphine- (15 mg/kg/day) pretreated animals. Furthermore, the mRNA expression level of CaMKII and BDNF increased significantly following ethanol administration in morphine-pretreated rats. Conversely, this improvement in spatial memory acquisition was prevented by daily subcutaneous administration of naloxone (2 mg/kg) 15 min prior to morphine administration. Our findings suggest that sub-chronic morphine treatment reverses ethanol-induced spatial memory impairment, which could be explained by modulating CaMKII and BDNF mRNA expressions in the hippocampus and amygdala.
有证据表明，成瘾和记忆系统是相关的，但这种相互作用的信号级联尚未完全阐明。钙调蛋白依赖性蛋白激酶 II（CaMKII）和脑源性神经营养因子（BDNF）在记忆过程中以及在药物成瘾中的重要性以前已经得到证实。在本研究中，我们研究了重复吗啡预处理对成年雄性大鼠系统给予乙醇引起的空间学习和记忆获得障碍的影响。此外，我们评估了这些药物暴露如何影响海马体和杏仁核中 CaMKII 和 BDNF 的表达水平。动物通过 8 次训练的单次训练课程进行训练，24 小时后进行包含 60 秒自由游泳而无平台的探针测试。在训练试验之前，大鼠每天接受一次皮下吗啡注射，持续 3 天，然后进行 5 天的洗脱期。结果表明，预训练乙醇（1g/kg）损害了空间学习和记忆获得，并下调了 CaMKII 和 BDNF 的 mRNA 表达。在吗啡（15mg/kg/天）预处理的动物中，乙醇的健忘作用受到抑制。此外，在吗啡预处理大鼠中，给予乙醇后 CaMKII 和 BDNF 的 mRNA 表达水平显著增加。相反，吗啡给药前 15 分钟每日皮下给予纳洛酮（2mg/kg）可阻止空间记忆获得的改善。我们的研究结果表明，亚慢性吗啡处理逆转了乙醇引起的空间记忆障碍，这可以通过调节海马体和杏仁核中 CaMKII 和 BDNF 的 mRNA 表达来解释。
