The olfactory bulbectomized rat model is not an appropriate model for studying depression based on morphological/stereological studies of the hippocampus

• Olfactory bulbectomized rat is a model of depression, but its validity is insufficient.
• The bulbectomy caused a reduction in the volumes of the CA1/2, CA3, and dentate gyrus.
• Fluoxetine did not reverse neuron loss in hippocampal regions after the bulbectomy.
• This model should not be used to detect the antidepressant activity of fluoxetine.

Bilateral olfactory bulbectomy (OBX) has been used as an animal model for major depression that results in behavioral, neurochemical, and neuroendocrinological changes were reversed by chronic treatment with antidepressants, including fluoxetine. However, both etiological and construct validities are lacking in OBX for rats. In the present study, we investigated the morphological changes in the hippocampi of rats undergoing OBX that were treated with fluoxetine (10 mg/kg, p.o. once daily for 4 and 12 weeks) using stereological techniques. Our results revealed that OBX caused a reduction in the volumes of the CA1/2, CA3, and dentate gyrus regions 4 weeks after OBX without fluoxetine treatment. With fluoxetine treatment, these reductions were achieved 12 weeks after OBX and the volumes were comparable to normal control rats. Nevertheless, fluoxetine treatment did not reverse neuron loss in all hippocampal regions 12 weeks after OBX. Therefore, we suggest that the OBX rat model should not be used to detect the antidepressant activity of various pharmacological agents such as fluoxetine.