Behavioral and biochemical studies of total furocoumarins from seeds of Psoralea corylifolia in the forced swimming test in mice.

The behavioral and biochemical effects of total furocoumarins from seeds of Psoralea corylifolia (TFPC) were investigated in the forced swimming test (FST) in mice in comparison with amitriptyline and fluoxetine. TFPC was found to reduce the duration of immobility in the FST without accompanying changes in ambulatory, rearing and grooming behaviors in the open-field test. After a 3-day treatment, TFPC at the doses from 7.5 to 100 mg/kg significantly decreased the immobility time. The efficacy of the higher doses exceeded that of amitriptyline at 10 and 20 mg/kg and fluoxetine at 13 mg/kg. After a 7- or 14-day treatment, TFPC exhibited an inverted U-shaped dose-response relations, maximal effects were obtained at 30 mg/kg, when the efficacy appeared to be more than that of amitriptyline and fluoxetine. In animal brain and liver, after 14-day treatment, TFPC significantly inhibited monoamine oxidase A and B (MAO-A and MAO-B) activities with an inverted U-shaped dose-dependent relationship in brain, and with dose-dependent relationship in liver. Moreover, TFPC was more potent for MAO-B than MAO-A, except at the lowest dose, which was similar to amitriptyline and fluoxetine. In addition, TFPC blocked plasma elevated cortisol level, an indicator of the hypothalamic-pituitary-adrenal (HPA) axis. TFPC significantly decreased liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level, two indicators of oxidative stress, providing an inverted U-shaped dose-dependent relationship. These results suggest that TEPC possesses potent antidepressant properties that are mediated via MAO activity, HPA axis action and oxidative stress in the FST in mice.