Background Anxiety is one the most common psychiatric disorders. Recently, anti-oxidants have been shown to possess anxiolytic properties. Objectives The present study aimed to investigate anxiolytic effect of ellagic acid (EA) in mice and its interaction with GABAA receptor. Materials and Methods 184 male albino mice (25 - 30 g) were randomly assigned into two subgroups (12 groups in each). In the first set of experiments, to evaluate acute administration of EA (single dose) on anxiety, experimental groups (10 groups, 8 mice per group) were control (received vehicle), EA-treated groups (received ellagic acid, 3, 10, 30 and 100 mg/kg, i.p.), diazepam (DZP)-treated groups (received DZP, 1, 3 and 5 mg/kg, i.p.), Flumazenil (FLZ) + diazepam-treated group (received FLZ, 3 mg/kg and + DPZ, 5 mg/kg, i.p.) and FLZ+EA-treated group (received FLZ, 3 mg/kg and ellagic acid, 30 mg/kg, i.p.). Moreover, in the first set of experiments, to evaluate the effect of chronic administration of EA on anxiety, experimental groups (2 groups, 8 mice per group) were control (received vehicle once a day for 10 days) and EA-treated group (received ellagic acid at the dose of 30 mg/kg, i.p. once a day for 10 days). In the second set of experiments, to evaluate acute (single dose) and chronic (for 10 days) administration of EA on motor activity, animal groupings were similar to the first set of experiment. Elevated plus maze (EPM) and open field tests used to study anxiolytic and motor activity effect of EA, respectively. Statistical analysis was performed by one-way ANOVA and post hoc Tukey’s test. P values less than 0.05 were considered as significant. Results Acute and chronic application of EA significantly enhanced the number of open arm entries and percentage of time spent in open arm compared with the control (P < 0.05). Pretreatment with flumazenil (FLZ + EA-treated group) significantly decreased the number of open arm entries and percentage of time spent in open arm compared with EA-treated group (only received EA at the dose of 30 mg/kg). Ellagic acid at the dose of 100 mg/kg significantly decreased ambulatory movement compared with the control, while EA at the dose of 30 mg/kg did not affect ambulation. Conclusions Acute and chronic administration of ellagic acid had anxiolytic property. Also, the most effective dose of ellagic acid was 30 mg/kg. Pretreatment with flumazenil reversed the beneficial effect of ellagic acid and diazepam on anxiety. It is likely that the anxiolytic effect of ellagic acid is largely mediated by activation of GABAA receptor
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