Several studies have evaluated thiazolidinedione therapy as medical treatments for some central nervous system disorders, such as cognitive deficits associated with neurodegenerative disorders. However, there is limited data to support a direct role for peroxisome proliferator-activated receptor-γ agonists in depression. Therefore, the aim of this study was to investigate antidepressant-like activity of rosiglitazone using the mouse tail suspension test and the rat forced swimming test, two models sensitive to the effects of antidepressants. In the tail suspension test, 5 days of treatment with rosiglitazone (8.5 or 17 mg/kg, orally) reduced immobility time. In the forced swimming test, rosiglitazone (6 or 12 mg/kg, orally) treatment decreased immobility time and increased climbing. These effects were not accompanied by any alteration in locomotor activity in the open field test. Rosiglitazone treatment (6 or 12 mg/kg, orally) significantly reduced plasma corticosterone levels in rats. GW9662 significantly inhibited the rosiglitazone-induced reduction in the duration of immobility.

In summary, this study suggests that rosiglitazone possesses a specific antidepressant-like activity in behavioral models and that this effect may be mediated by reduction of plasma corticosterone level.