Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2012 Sep;48(1):22-34. doi: 10.1007/s12031-012-9726-4. Epub 2012 Mar 3.
Recent studies show that morphine possesses protective preconditioning effects in different ischemia/reperfusion models. However, there is very little information about the antineuroinflammatory role of morphine and its protective effect against memory deficit. In the present study, we evaluated the role of morphine preconditioning in a model of mild neuroinflammation induced by intraperitoneal lipopolysaccharide (LPS) injection (1 mg/kg). Rats were trained on passive avoidance apparatus and challenged with LPS 20 h later. Four hours after LPS, rats were subjected to passive avoidance testing and then for the assessments of inflammatory and apoptotic cell death mediators in the hippocampus. LPS significantly increased the nuclear NF-κB and expression of COX-2, IL-1β, and TNF-α, augmented the activity of caspase-3 and PARP cleavage, and in parallel shortened the latencies to enter the dark compartment. Although morphine injection in a noninflammatory context was able to induce a neuroinflammatory response and memory loss, morphine preconditioning at the dose of 4 mg/kg significantly prevented the LPS-induced neuroinflammation and memory deficit. Morphine preconditioning was abolished by naloxone and, therefore, is dependent on opioid receptors. These results suggest that acute morphine injection, in spite of the induction of a neuroinflammatory response and amnesia per se, exerts an antineuroinflammatory role and protects from cell death and memory deficit in an inflammatory context.
最近的研究表明，吗啡在不同的缺血/再灌注模型中具有保护预处理效应。然而，关于吗啡的抗神经炎症作用及其对记忆缺陷的保护作用的信息却很少。在本研究中，我们评估了吗啡预处理在腹腔内注射脂多糖（LPS）（1mg/kg）诱导的轻度神经炎症模型中的作用。大鼠在被动回避装置上进行训练，并在 20 小时后接受 LPS 挑战。在 LPS 后 4 小时，大鼠进行被动回避测试，然后评估海马中的炎症和细胞凋亡死亡介质。LPS 显著增加了核 NF-κB 和 COX-2、IL-1β 和 TNF-α 的表达，增加了 caspase-3 的活性和 PARP 裂解，并平行缩短了进入暗室的潜伏期。尽管吗啡在非炎症环境下注射能够诱导神经炎症反应和记忆丧失，但吗啡预处理（4mg/kg）剂量可显著防止 LPS 诱导的神经炎症和记忆缺陷。纳洛酮消除了吗啡预处理，因此，吗啡预处理依赖于阿片受体。这些结果表明，急性吗啡注射，尽管本身会引起神经炎症反应和健忘症，但会发挥抗神经炎症作用，并在炎症环境中防止细胞死亡和记忆缺陷。
