Journal
NEUROSCIENCE LETTERS
Volume 426, Issue 1, Pages 54-58Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2007.08.054
Keywords
Tamiflu; Oseltamivir; abnormal behaviors; adverse reaction; drug interaction; avian influenza
Categories
Funding
- NIAAA NIH HHS [R01 AA012951-05, AA12951, R01 AA012951] Funding Source: Medline
- NIA NIH HHS [R01 AG018434, R01 AG018434-05, AG184334] Funding Source: Medline
- NIMH NIH HHS [R01 MH077791-02, R01 MH077791, MH077791] Funding Source: Medline
- NINDS NIH HHS [NS057105, P30 NS057105-03, P30 NS057105, P30 NS057105-039006] Funding Source: Medline
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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 (50 mg/kg, i.p.) produced no change in behavior within 2 h. However, prior injection of oseltamivir significantly altered the duration of loss of lightning reflex following ethanol injection (3.3 g/kg, i.p.). Ethanol injection in the presence of oseltamivir also resulted in enhanced hypothermia. In the CAI region of hippocampal slices, oseltamivir (100 mu M) induced paired-pulse facilitation in population spikes without changes in excitatory postsynaptic potentials. Similarly, 3 mu M 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 60 mM ethanol. These findings indicate that oseltamivir has effects on the central nervous system, especially when combined with other agents. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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