en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <strong>Introduction</strong>: Ethanol is considered as an effective agent in reducing brain stroke injury. In this study, we assessed the effects of modafinil along with ethanol as a combination therapy on behavioral function in Wistar rats.<br> <strong>Methods</strong>: The right Middle Cerebral Artery Occlusion (MCAO)&nbsp;was&nbsp;performed and the rats were divided into nine groups (n=8 per group). The animal groups in this study were as follows: 1. MCAO control group (ischemia without treatment); 2. vehicle group; 3. modafinil group that was randomly subdivided into three groups receiving different doses of modafinil (10, 30, and 100 mg/kg) for 7 days before MCAO; 4. ethanol group receiving 1.5 g/kg ethanol at the time of reperfusion; 5. modafinil + ethanol group that was further subdivided into three groups receiving modafinil at different doses (10, 30, and 100 mg/kg) for 7 days before MCAO and ethanol at the time of reperfusion. The motor behavior was measured using the Garcia test 24, 48, and 72 h after the ischemia, and the elevated body swing test was performed 48 and 72 h after the ischemia. The anxiety and locomotor activity were analyzed by open field test 48 and 72 h post-ischemia.<br> <strong>Results</strong>: The results showed that the neurological deficit score, locomotor activity, and unexpected thigmotaxis (anxiety) in the ethanol, modafinil (in a dose-dependent manner), and ethanol+modafinil treatment groups were significantly higher than the MCAO control group.&nbsp;<br> <strong>Conclusion</strong>: It seems that the combination therapy of modafinil (100 mg/kg) and ethanol (1.5 g/kg) significantly enhanced neuroprotection via an improvement in locomotor activity and neurological functions. Middle cerebral artery, Ethanol, Neuroprotection, Locomotion, Anxiety 269 278 http://bcn.iums.ac.ir/browse.php?a_code=A-10-618-7&slc_lang=en&sid=1 Yusef Abbasi yusef6542@gmail.com 13700319475328460027555 13700319475328460027555 No Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran. Kazem Mousavizadeh mousavik@gmail.com 13700319475328460027556 13700319475328460027556 No Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. & Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Ronak Shabani shabani.r@iums.ac.ir 13700319475328460027557 13700319475328460027557 No Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. & Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Majid Katebi majid.katebi@gmail.com 13700319475328460027558 13700319475328460027558 No Department of Anatomy, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Mehdi Mehdizadeh mehdizadeh.m@iums.ac.ir 13700319475328460027559 13700319475328460027559 Yes Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. & Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.