Background Stroke survivors commonly experience mood disturbances, such as depression (~30%) and anxiety (~25%). Post-stroke depression (PSD) and anxiety (PSA) commonly co-occur and can negatively impact stroke outcomes [1]. For example, they are linked to poorer functional and cognitive recovery, poorer quality of life, and higher mortality rates. Unfortunately, PSD and PSA are usually undertreated and many cases may remain undiagnosed. Animal models can be helpful in answering remaining questions about the pathophysiology, developing diagnostic tools, and optimizing treatment strategies. Current models, using middle cerebral artery occlusion, may be confounded by associated motor deficits that can affect tests of depression and anxiety [2]. Additionally, preclinical research focuses mainly on PSD, leaving PSA somewhat understudied. The vasoconstrictor endothelin-1 (ET-1) can be used to induce small strokes in specific brain areas associated with anxiety- and depressive-like behavior, without affecting motor function [3]. For example, lesions in the prefrontal-subcortical circuit are commonly associated with PSD and PSA. A recent study showed anxiety- and depression-like symptoms in mice up to 6 weeks following ET-1 injection into the medial prefrontal cortex [4]. Methods To induced a unilateral ischemic lesion in the medial prefrontal cortex, adult male Sprague-Dawley rats (n=8) were injected with 1 µ ET-1 (400 pmol) at the following coordinates: anterior/posterior +3.0, medial/lateral -1.3, and dorsal/ventral -3.5 (all coordinates relative to bregma). Sham-operated animals (n=8) were injected with artificial cerebral spinal fluid. Animal behavior was evaluated at 2 and 6 weeks post stroke using Open Field (OF), Horizontal Ladder Test (HLT), Elevated Plus Maze (EPM), and Forced Swim Test (FST). Data, presented as mean ± standard error of the mean, was analyzed using t-test (IBM SPSS Statistics 22). Results Preliminary results suggest that, at 2 weeks, stroke rats spent significantly less time in the open arms of the EPM compared to sham rats (9.2% ± 2.4 vs. 20.2% ± 3.1, as percentage of total time, p = 0.015), indicating more anxiety-like behavior. There were no effects on motor function as measured in the OF and the HLT. (In contrast to X), we found no difference in depressive-like behavior in the FST between stroke and sham animals. At 6 weeks, the anxiety-like phenotype could not be detected anymore (18.2% ± 3.4 vs 21.7% ± 3.5, p > 0.05). Additionally, no differences were found in motor function (OF and HLT) and depressive-like behavior FST. Conclusions To our knowledge, this is the first study specifically evaluating anxiety- and depressive-like behavior in rats following a unilateral endothelin-1-induced lesion in the medial prefrontal cortex. Our results show that a unilateral injection of ET-1 lead to anxiety-, but not depressive-like behavior in rats. This might suggest that damage to a secondary brain area may be necessary in order to induce a depression phenotype.