Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy.

Olfactory bulbectomy is an established animal model of depression that has been mostly investigated in rats. As in human major depression, bulbectomy induces behavioral alterations that can be ameliorated by chronic antidepressant treatment. Furthermore, bulbectomy in rats is known to induce neurodegeneration in some brain areas. The aim of the present study was to evaluate patterns of behavioral alterations and neurodegeneration, and their drug-induced reversibility, in bulbectomized mice. Our results reveal that in mice bulbectomy increases locomotor activity and induces deficits in the passive avoidance test, comparable to the effects seen in rats. Bulbectomy also induced neuronal degeneration, visualized by incorporation of Fluoro-Jade B, in the piriform cortex and the posterolateral cortical amygdaloid nucleus (PLCo). Chronic treatment with the antidepressant amitriptyline protected neurons in both areas and efficiently reversed abnormal locomotor activity induced by bulbectomy. Treatment with citalopram was effective in reversing the behavioral deficits induced by bulbectomy, but did not protect against neurodegeneration. Our data indicate significant overlap between mice and rats in terms of behavioral alterations and neurodegeneration following olfactory bulbectomy. However, there are differences in drug-mediated reversibility of neurodegeneration suggesting that neurodegeneration and protection may be "second-order" features in this animal model of depression. This may also be relevant in the context of studies using genetically altered mice.