Effects of intranasal irrigation with mitotic inhibitors on olfactory behavior and biochemistry in mice

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.