Oseltamivir (
Tamiflu) is now being stockpiled by several governments as a first line treatment for an anticipated outbreak of
avian influenza caused by H5N1. However, abnormal behaviors and death associated with the use of
Tamiflu have developed into a major issue in Japan where
Tamiflu is often prescribed for seasonal
influenza. Thus, it is critical to determine neuropsychiatric effects of
oseltamivir and to establish methods for safe administration. Using juvenile rats and rat hippocampal slices, we investigated whether
oseltamivir has adverse effects on the central nervous system. Systemic injection of
oseltamivir (50mg/kg i.p.) produced no change in behavior within 2h. However, prior injection of
oseltamivir significantly altered the duration of loss of lightning reflex following
ethanol injection (3.3g/kg, i.p.).
Ethanol injection in the presence of
oseltamivir also resulted in enhanced
hypothermia. In the CA1 region of hippocampal slices,
oseltamivir (100 microM) induced paired-pulse facilitation in population spikes without changes in excitatory postsynaptic potentials. Similarly, 3 microM
oseltamivir carboxylate, the active metabolite of
oseltamivir, facilitated neuronal firing, though the facilitation did not involve GABAergic disinhibition. Moreover,
oseltamivir carboxylate produced further facilitation following administration of 60mM
ethanol. These findings indicate that
oseltamivir has effects on the central nervous system, especially when combined with other agents.