Role of serotonergic system on modulation of depressogenic-like effects of silymarine.

In the present study, we have investigated the effects of silymarine on depression and the possible role of serotonergic system in these effects. The rats were anesthetized intraperitoneally with ketamine hydrochloride and placed in a Stoelting stereotaxic instrument. A stainless steel guide cannula (22-gauge) was implanted in the third ventricular region. The third ventricular region was infused by means of an internal cannula (27-gauge), terminated 1 mm below the tip of the guide cannula. Forced swimming test was used for evaluating the depression. The results obtained from this study showed that oral administration of silymarin (35, 70, 140 and 280 mg/rat) for two weeks increased the immobility time in forced swimming test, indicating an increase in depression level of the treated rats. Intra-third-ventricle (Intra-TV) infusion of 5HT1A receptor agonist 8-OH-DPAT (25 and 10 ng/rat) decreased the immobility time indicating an anti-depression effect, while injection of 5HT1A receptor antagonist NAN190 (0.25, 0.5 and 1 μg/rat) had no significant effect on immobility time. An effective dose of 8-OH-DPAT (10 ng/rat) co-administered with silymarin (140 and 280 mg/rat) decreased the depressogenic effects of silymarin. These results showed that the depressogenic effects of silymarin may be modulated via 5HT1A receptor of serotonin.