Potentiation of the antidepressant-like effect of desipramine or reboxetine by metyrapone in the forced swimming test in rats.

The obtained results revealed that joint administration of desipramine or reboxetine and metyrapone (a glucocorticoid synthesis inhibitor) had more potent antidepressant-like activity in the forced swimming test (FST) in rats compared to treatment with either drug alone. WAY100636 (a 5-HT(1A) antagonist), and prazosin (an alpha(1)-adrenergic antagonist), used in doses ineffective in the FST, inhibited the antidepressant-like effect induced by co-administration of desipramine (10 mg/kg) or reboxetine (10 mg/kg) and metyrapone (50 mg/kg). The above-mentioned findings suggest that, among other mechanisms, the 5-HT(1A) and alpha(1)-adrenergic receptors may play a role in this effect. Furthermore, they may be of particular importance to the pharmacotherapy of drug-resistant depression.