Time course of alterations after olfactory bulbectomy in mice

Olfactory bulbectomy in rodents causes behavioral alterations, which result in a model of depression, validated for pharmacological screening of antidepressant drugs. To unravel the appearance and time course of the major behavioral effects which follow surgery, mice underwent olfactory bulb ablation or sham operation, and were analyzed after 1, 2, or 4 weeks. Bulbectomized (BX) mice were anosmic, and hyperactive when tested under stressful situations in the forced swimming test. Predatory aggression was upregulated in a time-dependent way: only after 4 weeks BX mice were faster than controls in attacking prey. At the same time, they were less aggressive against intruders; they did not differ from controls in open field exploration, but displayed a cognitive impairment in water maze. Behavioral tests thus indicated a marked hyperreactivity, a dissociation among different aggressive behaviors, and also a cognitive impairment induced by bulbectomy. Histological confirmation of the damage revealed that major modifications took place in the rostral pole of frontal lobes, with a significant increase in the width of the rostral migratory stream, 2 weeks after surgery, and in the subventricular zone, 4 weeks after surgery. These results suggest a base for the time-course of appearance of behavioral symptoms in BX mice.