Antidepressant-like effect of gallic acid in mice: Dual involvement of serotonergic and catecholaminergic systems

Aims: This study was planned to examine the antidepressant potency of gallic acid (30 and 60 mg/kg), a phenolic acid widely distributed in nature, together with its possible underlying monoaminergic mechanisms. Main methods: Antidepressant-like activity was assessed using the tail suspension (TST) and the modified forced swimming tests (MFST). Locomotor activity was evaluated in an activity cage. Key findings: Administration of gallic acid at 60 mg/kg reduced the immobility duration of mice in both the TST and MFST without any changes in the locomotor activity. The anti-immobility effect observed in the TST was abolished with pre-treatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100 mg/kg i. p. administered for 4-consecutive days), ketanserin (a 5-HT2A/2C antagonist; 1 mg/kg i. p.), ondansetron (a 5-HT3 antagonist; 0.3 mg/kg i. p.), alpha-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100 mg/kg i. p.), phentolamine (non-selective alpha-adrenoceptor antagonist; 5 mg/kg i. p.), SCH 23390 (a dopamine D1 antagonist; 0.05 mg/kg s. c.), and sulpiride (a dopamine D2/D3 antagonist; 50 mg/ kg i. p.). However, NAN 190 (a 5-HT1A antagonist; 0.5 mg/kg i. p.) and propranolol (a non-selective beta-adrenoceptor antagonist; 5 mg/kg i. p.) pre-treatments were ineffective at reversing the antidepressant-like effects of gallic acid. Significance: The results of the present study indicate that gallic acid seems to have a dual mechanism of action by increasing not only serotonin but also catecholamine levels in synaptic clefts of the central nervous system. Further alpha adrenergic, 5-HT2A/2C and 5-HT3 serotonergic, and D1, D2, and D3 dopaminergic receptors also seem to be involved in this antidepressant-like activity.