Lithium affects rat hippocampal electrophysiology and epileptic seizures in a dose dependent manner

•Lithium, a mood stabilizer, prevents apoptosis-dependent cellular death and is used to treat various neurological disorders.•At a low dose (10 mg/kg), lithium attenuates susceptibility to and the severity of pilocarpine-induced seizures.•At a higher dose (40 mg/kg), lithium exhibits the opposite ef...

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Published in:Epilepsy research 2018-10, Vol.146, p.112-120
Main Authors: Jiang, Guohui, Pu, Tianqiang, Li, Zhimin, Zhang, Xiaodong, Zhou, Ruijiao, Cao, Xing, Yu, Juming, Wang, Xiaoming
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Language:English
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Epileptic discharges
Epileptic seizures
Hippocampal electrophysiology
Lithium
Power spectrum
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description •Lithium, a mood stabilizer, prevents apoptosis-dependent cellular death and is used to treat various neurological disorders.•At a low dose (10 mg/kg), lithium attenuates susceptibility to and the severity of pilocarpine-induced seizures.•At a higher dose (40 mg/kg), lithium exhibits the opposite effect; this may be related to suppression of gamma oscillation.•The low-dose effect is likely due to increased theta and gamma oscillation and reduced ripple activity. 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 
doi_str_mv 10.1016/j.eplepsyres.2018.07.021
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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 &lt; 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 &lt; 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. 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Conversely, when the dose was increased to 40 mg/kg, lithium reduced the frequency of lower-class seizures compared to control treatment (p &lt; 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. 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Conversely, when the dose was increased to 40 mg/kg, lithium reduced the frequency of lower-class seizures compared to control treatment (p &lt; 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. 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subjects Epileptic discharges
Epileptic seizures
Hippocampal electrophysiology
Lithium
Power spectrum
title Lithium affects rat hippocampal electrophysiology and epileptic seizures in a dose dependent manner
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