¹Division of Pharmacology and Toxicology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran DOI : 10.29228/jrp.323 The coronavirus spreading has led to the development of many drugs to prevent and treat it. One of these drugs is hydroxychloroquine, so this study was designed to investigate the potential side effects of the drug when used long-term and at high doses in male rats. Physiologically, 30 male Wistar rats were randomly divided into two groups: control and hydroxychloroquine (10, 50, 100, and 200 mg/kg) (n=6 per group). Hydroxychloroquine was administered orally for seven consecutive days. On the seventh day, 30 minutes after receiving hydroxychloroquine, the animals were anesthetized with a combination of ketamine (70 mg/kg) and xylazine (7 mg/kg), the animal's head was fixed using a stereotaxic device, and an incision 1.5-2 cm long was made in the scalp. Drill the desired point with a perforated dental drill using the Paxinos coordinates (AP = -0.27, ML = -0.14, DV = -0.3). Pentylenetetrazol (80 mg/kg i.p.) was used to induce epileptiform activities. Finally, diazepam (10 mg/kg, i.p.) was given to reduce epileptiform activity. The number of seizure activities was reduced significantly (p<0.001) at dose of 10 mg/kg and significantly (p<0.001) increased at doses of 100 and 200 mg/kg. In contrast, the dose of 50 mg/kg had no discernible effect. Giving male rats high doses of oral hydroxychloroquine for one week has biphasic effects on the number of pentylenetetrazol-induced seizure activities. As a result, it has protective effects in low and stimulant effects in high doses. Keywords : CA1, in vivo; epileptiform activity, rat