Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat

Olfactory bulbectomy is one of the most validated models of depression. We demonstrate that bilateral removal of the olfactory bulbs in rats produced a significant decline of allopregnanolone content in a select cerebrocortical area which was reversed by chronic (3-week) treatment with three different classes of antidepressant (desipramine, fluoxetine, and sertraline, and venlafaxine). The effects of the chronic antidepressant treatments on allopregnanolone cortical content are observed at a time which typically coincides with the drug's abilities to reverse the behavioral deficits of the bulbectomy syndrome. We therefore propose that normalization of allopregnanolone cerebrocortical levels may contribute to the antidepressant-like profile of these drugs in the olfactory-bulbectomized rat model of depression.