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Abstract: Free and Easy Wanderer Plus (FEWP) is a well-known traditional Chinese medicine that has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether FEWP could ameliorate stress-associated behavior in rats. Following the exposure to enhanced single prolonged stress (ESPS) paradigm, consisting of 2-hr constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, animals were administered orally with FEWP (2.5, 5, or 10mg/kg daily) or vehicle for 2weeks. Animals were then tested in the open field, elevated plus-maze, and Morris water maze. ESPS exposure resulted in pronounced anxiety-like behavior, without impairing locomotor activity, as indicated by significant decreases of time spent and number of entries into open arms in the elevated plus-maze test, and unaltered distance traveled in the open field test compared to unexposed animals. ESPS-exposed animals also displayed marked cognitive impairments, with significant increases of distance traveled and the escape latency to the underwater platform, and a striking decrease of time spent in the target quadrant with and without the removal of the platform in the water maze test. However, repeated treatment with FEWP, particularly at higher doses, reversed the aforementioned behavioral values in the elevated plus-maze and water maze tests to the levels similar to unexposed animals. These results indicate that FEWP possesses anxiolytic and cognition-improving effects and may be an effective herbal preparation for the treatment of stress-associated conditions, such as posttraumatic stress disorder (PTSD). [Copyright &y& Elsevier]