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Introduction: Fennel is rich in phytoestrogens and is used for estrogen deficiency disorders. Estrogens affect anxiety through neurochemical systems such as GABA-A receptors. In this study the effects of fennel on GABA-A and estrogen receptors in anxiety were investigated. Methods: Adult female Wistar rats weighing (180±20 g) were divided into 8 groups. Groups received saline, fennel (200, 500, 750 mg/kg), tamoxifen (15 mg/kg) + fennel (500 mg/kg), picrotoxin (1 mg/kg) + fennel (500 mg/kg). A control group was also used. Elevated plus maze was used for evaluation of anxiety by measuring the time spent in the open arm. All drugs were administered intraperitoneally. Results: The results showed that fennel only at the dose of 500 mg/kg had significant anxiolytic effects and increased the time spent in open arms (P<0.01). Picrotoxin (GABA-A antagonist) significantly prevented anxiolytic effect of 500 mg/kg of fennel (P<0.001). Tamoxifen, an estrogen receptor antagonist, also abolished the anxiolytic effect of fennel (P<0.001). Conclusion: Fennel reduced anxiety in rats and picrotoxin, a non-competitive antagonist of GABA-A receptors, as well as tamoxifen, an antagonist/agonist of estrogen receptors, reduced this anxiolytic effect. Thus fennel as a herbal drug seems to have an anxiolytic effect and it probably acts through GABA-A and estrogen receptors.

Keywords: Key words: Anxiety, Fennel, Tamoxifen, Picrotoxin, Elevated Plus Maze

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