Introduction: Epilepsy is a set of chronic neurological disorders characterized by seizures associated with abnormal and uncontrolled neuronal activity of the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter-2 (EAAT2), one of the major glutamate transporters, is responsible for total glutamate intake. Ceftriaxone is a β-lactam antibiotic that increases EAAT-2 expression and functional activity. This study aims to investigate the effects of ceftriaxone on penicillin-induced epileptiform activity by using electrocorticography (ECoG) in anesthetized rats.
 Materials and Methods: In this study, 35 Wistar male rats were used. The rats were divided into five groups of 7. In group 1, 2.5 μL 500 IU of penicillin intracranially (i.c.) and 1 ml saline solution and intraperitoneally (i.p.) were given, respectively. In group 2, 200 mg/kg, i.p. of ceftriaxone was administered 30 minutes after penicillin. In group 3, 400 mg/kg of ceftriaxone was administered i.p. 30 minutes after penicillin. 500 mg/kg of sodium valproate was administered i.p. following 30 minutes of penicillin in group 4. In group 5, 400 mg/kg, i.p. of ceftriaxone and 500 mg/kg, i.p. of sodium valproate were administered 30 minutes after penicillin. The rats were placed in a stereotaxic device after the procedure, and electrocorticogram recordings were captured for 180 minutes.
 Results: The acute treatment of ceftriaxone reduced spike-wave frequency and spike-wave amplitude of penicillin-induced epileptiform activity in the rats. 
 Conclusion: These findings suggest that acute ceftriaxone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Ceftriaxone may has an anti-epileptogenic potential.
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