The effect of fluoxetine on penicillin-induced epileptiform activity.

AIM: Depression is the most frequent psychiatric comorbidity in patients with epilepsy. Fluoxetine is the most widely used selective serotonin reuptake inhibitor (SSRI) in depression. The aim of the present study was to evaluate the dose-dependent effect of fluoxetine on penicillin-induced seizure by electrocorticogram (ECoG), a model for simple partial epilepsy.

METHOD: The epileptiform activity was induced by intracortical (i.c.) microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 5, 10, or 20 mg/kg doses of fluoxetine were administered intraperitoneally (i.p.). An ECoG recording was performed for 180 min using the data acquisition system. The frequency and the amplitude of the epileptiform activity were analyzed.

RESULTS

Penicillin induced bilateral spikes and spike-wave complexes within 2-5 min. The 5 and 10 mg/kg doses of fluoxetine significantly reduced the frequency (58%, p < 0.05 and 69%, p < 0.01, 40 and 50 min after fluoxetine injection, respectively) and amplitude (60%, p < 0.01 and 73%, p < 0.05, 40 and 120 min after fluoxetine injection, respectively) of epileptiform activity compared with penicillin-induced seizure group (control). Five-milligram fluoxetine (i.p.) was the most effective dose to decrease frequency and amplitude on penicillin-induced epileptiform activity. However, a higher fluoxetine dose (20 mg/kg) significantly increased frequency (147%, p < 0.01) and amplitude (123%, p < 0.05) of epileptiform activity 40 and 120 min after fluoxetine administration compared with control group. Also, bursts of population spikes were seen in 20 mg/kg fluoxetine doses.

CONCLUSION

Results of the present study indicate that low and moderate fluoxetine doses have an anticonvulsant effect while high doses have proconvulsant effect on penicillin-induced epileptic activity.