Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementia

“…Surprisingly, treatment with low doses was found to significantly increase the levels of PPR in ISIs 50 ms to 175 ms with respect to the 2VO+V group. The I/O curve is an index for the evaluation of basal neuronal excitability, reflecting both the level of presynaptic neurotransmitter release and postsynaptic processes [ 31 ]. The depression of PPR indicates that the initial release probability was high.…”

Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerability

“…It also can increase the GABAergic neuron activity and decrease glutamatergic neuron function. This model could result in the suppression of neurons and lessen seizure occurrence (Meehan et al , 2011; Kaminski et al , 2012; Pichardo-Macías et al , 2016; González et al , 2020). A correlation between levetiracetam and improving rats’ manic symptoms was also shown in a previous animal study (Lamberty et al , 2001).…”