The authors have withdrawn this preprint due to author disagreement.
Background Levetiracetam (LEV), an antiepileptic drug, has been recently demonstrated to improve the cognitive function. Hippocampal theta rhythm (4–12 Hz) is associated with a variety of cognitively related behaviors, such as exploration, locomotion and spatial memory in both humans and animal models. We investigated the effects of LEV on the theta rhythm in the rat hippocampal CA3 area. Results We found that LEV increased the power of theta oscillation in a dose-dependent manner. The increase in theta power can be blocked by GABAA receptor or NMDA receptor antagonists but not by AMPA receptor antagonist, indicating the involvement of GABAA receptor and NMDA receptor in the induction of theta activity. Interestingly, LEV enhancement of theta power can be also blocked by taurine, indicating that LEV induction of theta may be related to the indirect boosting of GABA action via reduction of extrasynaptic GABAA receptor activation. Furthermore, the increased theta power can be partially reduced by mACh receptor antagonist atropine but not by nACh receptor antagonists, suggesting that mACh receptor activation provides excitatory input into local network responsible for LEV induction of theta. Conclusions Our study demonstrated that induction of a synchronized network oscillation, a novel role of LEV may especially benefit for the treatment of the neuronal disorders with impaired theta oscillation and cognitive function.
Background Levetiracetam (LEV), an antiepileptic drug, has been recently demonstrated to improve the cognitive function. Hippocampal theta rhythm (4–12 Hz) is associated with a variety of cognitively related behaviors, such as exploration, locomotion and spatial memory in both humans and animal models. We investigated the effects of LEV on the theta rhythm in the rat hippocampal CA3 area. Results We found that LEV increased the power of theta oscillation in a dose-dependent manner. The increase in theta power can be blocked by GABAA receptor or NMDA receptor antagonists but not by AMPA receptor antagonist, indicating the involvement of GABAA receptor and NMDA receptor in the induction of theta activity. Interestingly, LEV enhancement of theta power can be also blocked by taurine or THIP, indicating that LEV induction of theta may be related to the indirect boosting of GABA action via reduction of extrasynaptic GABAA receptor activation. Furthermore, the increased theta power can be partially reduced by mACh receptor antagonist atropine but not by nACh receptor antagonists, suggesting that mACh receptor activation provides excitatory input into local network responsible for LEV induction of theta. Conclusions Our study demonstrated that induction of a synchronized network oscillation, a novel role of LEV may especially benefit for the treatment of the neuronal disorders with impaired theta oscillation and cognitive function.
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