Antidepressant-like effect of low molecular proanthocyanidin in mice: Involvement of monoaminergic system

Proanthocyanidin is a phenolic product present in plants which has antioxidant, antinociceptive and neuroprotective properties, without inducing significant toxicological effects. The present study tested the hypothesis that low molecular proanthocyanidin from grapes that has optimized bioavailability, would exert antidepressant-like activities in behavioral despair tests. The results suggested that oral administration proanthocyanidin at doses of 25 and 50 mg/kg for 7 days significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. The doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical and neuropharmacological assays showed that proanthocyanidin produced a marked increase of 5-HT levels at 25 and 50 mg/kg in three brain regions, the frontal cortex, hippocampus and hypothalamus. Noradrenaline and dopamine levels were also increased when higher dose of proanthocyanidin (50 mg/kg) administration both in the frontal cortex and hippocampus. These effects were similar to those observed for the classical antidepressant imipramine (10 mg/kg, i.p.). Moreover, Our study suggested that proanthocyanidin (12.5, 25 and 50 mg/kg) dose dependently inhibited monoamine oxidase-A (MAO-A) activity, while MAO-B inhibitory activity was also found at higher doses (25 and 50 mg/kg) after 7 days administration. MAO-A selective inhibitor, moclobemide (20 mg/kg, i.g.) produced MAO-A inhibition of 70.5% in the mouse brain. These findings suggest that the antidepressant-like effects of proanthocyanidin may involve the central monoaminergic neurotransmitter systems.