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The infralimbic cortex (IL) regulates anxiety-like behavior in rats.IL stimulation increases open arm entries in the elevated plus-maze.Prelimbic cortex stimulation does not induce significant behavioral changes.Multiunit activity of the IL increases prior to entry from closed to open arms.The IL may be involved in overcoming anxiety-like behavior in rats.Fear and anxiety affect the activities of daily living and require concerted management, such as coping strategies, to preserve quality of life. The infralimbic (IL) and prelimbic (PL) medial prefrontal cortices have been implicated in the regulation of fear- and anxiety-like behavior, but their roles in overcoming fear- and anxiety-like behavior remain unknown. We investigated the anxiolytic-like effects of electrical stimulation of the IL and PL cortices in rats during the elevated plus-maze test. IL stimulation led to a significantly higher percentage of time spent and entries in the open arms, whereas PL stimulation did not have any significant behavioral effects. Subsequently, we recorded multiunit activity from the IL and PL cortices in rats using a wireless telemetry device, to determine whether activation of the IL occurs when rats enter the open arms in the elevated plus-maze test. The firing rate of IL neurons increased 1–3s prior to entry from the closed arm to the open arm, whereas there were no corresponding changes in the firing rate of PL neurons. Taken together, the present findings suggest that the IL plays a key role in exerting active action to overcome anxiety-like behavior.