Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

BACKGROUND Oseltamivir phosphate (OP, Tamiflu(®)) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. OBJECTIVE The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. METHODS Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 10(5) plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. RESULTS We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. CONCLUSION Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.