Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

Introduction: 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. Methods: The right Middle Cerebral Artery Occlusion (MCAO) was 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. Results: 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.  Conclusion: 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.