Harding J W, Wright J W
Brain Res. 1979 May 18;168(1):31-41. doi: 10.1016/0006-8993(79)90126-4.
Mice were trained to find buried food pellets or amyl acetate-scented sugar cubes. After training, the mice were intranasally irrigated with saline or one of several mitotic inhibitors--hydroxyurea (10 mM), ethidium bromide (2 mM), cytosine arabinoside (10 mM), or colchicine (0.25 mM). The behavioral testing was continued daily. By day 6 the colchicine animals had completely lost their ability to find sugar cubes. By day 8 all the ethidium bromide animals had lost their ability to find food pellets although 20% could still find the sugar cubes. The hydroxyurea animals exhibited a less dramatic and temporary deficit in olfactory capabilities which peaked near day 8. Cytosine arabinoside had no effect on olfactory-mediated behavior. The testing was terminated at 21 days. Two days later the animals were killed, olfactory tissue removed and assayed for thymidine incorporation into macromolecules, and the chemoreceptor marker, carnosine synthetase. All groups had a reduction in thymidine incorporation (33-25%). The ethidium bromide and colchicine groups exhibited a dramatic decrease in carnosine synthetase activity (ethidium bromide--olfactory bulb = 8% control, epithelium = 2%; colchicine--olfactory bulb = 10%, epithelium, 108%). These data are consistent with the notion that a functional mitotic process is necessary for continued olfactory capabilities and that in interruption in the normal mitotic process results in a decrease in olfactory chemoreceptor neurons and a loss in function.
小鼠被训练寻找埋在地下的食物颗粒或醋酸戊酯香味的糖块。训练后，给小鼠鼻腔内灌注生理盐水或几种有丝分裂抑制剂之一——羟基脲（10 mM）、溴化乙锭（2 mM）、阿糖胞苷（10 mM）或秋水仙碱（0.25 mM）。行为测试每天持续进行。到第6天，用秋水仙碱处理的动物完全丧失了寻找糖块的能力。到第8天，所有用溴化乙锭处理的动物都丧失了寻找食物颗粒的能力，尽管20%的动物仍能找到糖块。用羟基脲处理的动物嗅觉能力出现了不太显著且短暂的缺陷，在第8天左右达到峰值。阿糖胞苷对嗅觉介导的行为没有影响。测试在21天结束。两天后处死动物，取出嗅觉组织，检测胸苷掺入大分子的情况以及化学感受器标记物肌肽合成酶。所有组胸苷掺入量均减少（33% - 25%）。溴化乙锭和秋水仙碱组肌肽合成酶活性显著降低（溴化乙锭——嗅球 = 对照的8%，上皮 = 2%；秋水仙碱——嗅球 = 10%，上皮 = 108%）。这些数据与以下观点一致，即功能性有丝分裂过程对于持续的嗅觉能力是必要的，并且正常有丝分裂过程的中断会导致嗅觉化学感受器神经元减少和功能丧失。
