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.

Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression.

Allopregnanolone (ALLO) is one of the most potent positive endogenous allosteric modulators of the type A gamma-aminobutyric acid (GABA(A)) receptors. While the robust anxiolytic profile of ALLO has been extensively characterized in rodents and its antidepressant-like effect was recently demonstrated in mice, there have been only few reports on alterations of brain ALLO levels in putative animal models of depression and anxiety. Removal of the olfactory bulbs of rats produces one of the most predictive animal models with which to screen for drugs with potential antidepressant activity following repeated treatment.