Vucković Marta G, Wood Ruth I, Holschneider Daniel P, Abernathy Avery, Togasaki Daniel M, Smith Alexandra, Petzinger Giselle M, Jakowec Michael W
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90033, USA.
Neurobiol Dis. 2008 Nov;32(2):319-27. doi: 10.1016/j.nbd.2008.07.015. Epub 2008 Aug 5.
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson's disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear extinction compared to controls. High Performance Liquid Chromatography analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light-dark preference, or hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain.
1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)损伤的小鼠可作为基底神经节损伤和帕金森病的模型。本研究调查了MPTP诱导的损伤对联想记忆、条件性恐惧和情感行为的影响。给雄性C57BL/6小鼠注射生理盐水或MPTP,并在损伤后7天或30天对不同组进行评估。在食物偏好的社会传递测试中,与对照组相比,MPTP处理后30天的小鼠对熟悉食物的偏好显著降低。与对照组相比,MPTP损伤后7天和30天的小鼠恐惧消退增加。组织匀浆的高效液相色谱分析表明,纹状体、额叶皮质和杏仁核中的多巴胺和5-羟色胺减少。通过悬尾试验、蔗糖偏好试验、明暗偏好试验或洞板试验未检测到焦虑或抑郁的变化。总之,小鼠急性MPTP损伤方案会导致联想记忆和条件性恐惧受损,无情绪变化,且全脑多巴胺和5-羟色胺减少。