Tramullas Mónica, Martínez-Cué Carmen, Hurlé María A
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Neuropharmacology. 2008 Mar;54(4):640-52. doi: 10.1016/j.neuropharm.2007.11.018. Epub 2007 Dec 8.
Several studies open up the possibility that chronic exposure to opioid drugs in the CNS would interfere with learning and memory through a neurotoxic effect related to activation of apoptotic pathways. Here, we have analyzed the effects of prolonged heroin administration on sensorimotor and cognitive performance in mice, as well as the associated changes in brain expression of proteins regulating the extrinsic (FasL and Fas) and the mitochondrial (Bcl-2, Bcl-X(L), Bad and Bax) apoptotic pathways. Our findings indicate that chronic heroin did not interfere with mice performance in a battery of sensorimotor tests. On the other hand, cognitive ability in the Morris water maze and cognitive flexibility-related performance were strongly impaired by chronic heroin. These effects were associated with up-regulation of pro-apoptotic proteins such as Fas, FasL and Bad, in the cortex and hippocampus, indicating the activation of both the death receptor and the mitochondrial apoptotic pathways. Another indicator of apoptosis was the presence of TUNEL (TdT-mediated dUTP nick-end labeling) positive cells scattered throughout the brain.
多项研究揭示了这样一种可能性，即中枢神经系统中长期接触阿片类药物可能通过与凋亡途径激活相关的神经毒性作用干扰学习和记忆。在此，我们分析了长期给予海洛因对小鼠感觉运动和认知能力的影响，以及调节外在（FasL和Fas）和线粒体（Bcl-2、Bcl-X(L)、Bad和Bax）凋亡途径的蛋白质在大脑中的表达变化。我们的研究结果表明，慢性给予海洛因并未干扰小鼠在一系列感觉运动测试中的表现。另一方面，慢性给予海洛因严重损害了小鼠在莫里斯水迷宫中的认知能力以及与认知灵活性相关的表现。这些影响与皮质和海马中促凋亡蛋白如Fas、FasL和Bad的上调有关，表明死亡受体和线粒体凋亡途径均被激活。凋亡的另一个指标是在整个大脑中散在分布的TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）阳性细胞的存在。
