Lithium, a classic mood stabilizer, prevents apoptosis-dependent cellular death and has garnered considerable interest as a
neuroprotective agent that is efficacious in the treatment of many neurological diseases. However, the effects of
lithium in
epilepsy remain controversial. We found that different doses of
lithium affect epileptic seizure activity and bidirectionally modulate the susceptibility to and severity of
seizures induced by
pilocarpine in rats. Recently, it has been demonstrated that systematically administered
lithium affects the powers of hippocampal gamma and theta oscillations in baseline electroencephalograms. Low-dose
lithium (10 mg/kg) administered to
pilocarpine-treated rats markedly increased the powers of basal gamma (30-80 Hz) and theta (4-12 Hz) oscillations, decreased the proportion of Racine stage 4-5
seizures, extended latency until seizure onset, and significantly reduced the frequency of lower-class
seizures (p < 0.05). Conversely, when the dose was increased to 40 mg/kg,
lithium reduced the frequency of lower-class
seizures compared to control treatment (p < 0.05). Further, at this high dose,
lithium reduced the power of basal gamma oscillations and markedly increased the susceptibility to and severity of
pilocarpine-induced
seizures and enhanced ripple rhythms (80-200 Hz) postictally. Our results provide a framework for further investigations of the underlying electrophysiological mechanisms of
lithium-induced imbalances in excitatory and inhibitory neural circuits that regulate seizure activity in rats. In conclusion, the observed in vivo changes in the powers of basal gamma and theta oscillations in response to different doses of
lithium may reflect hippocampal neural network responsiveness.