TY - JOUR
T1 - Effect of levetiracetam on extracellular amino acid levels in the dorsal hippocampus of rats with temporal lobe epilepsy
AU - Luz Adriana, Pichardo Macías
AU - Blanca Alcira, Ramírez Mendiola
AU - Itzel Jatziri, Contreras García
AU - Sergio Roberto, Zamudio Hernández
AU - Juan Luis, Chávez Pacheco
AU - Karla Berenice, Sánchez Huerta
AU - Julieta Griselda, Mendoza Torreblanca
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/2
Y1 - 2018/2
N2 - Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy. Epileptic rats developed clear signs of hyperexcitability, i.e., an elevated Glu/GABA ratio in the DH. The LEV concentration in blood after 7 days of treatment was within the therapeutic range. In contrast, LEV was not detected four days after mini-pump removal (washout period). Furthermore, LEV restored the Glu/GABA ratio to approximately the control level and significantly increased the GABA concentration after the initiation of high-K+ conditions. Based on these data, LEV treatment restored the lost balance between the excitatory and inhibitory systems under basal conditions. Moreover, LEV showed a selective effect by preferentially increasing vesicular release of GABA, a mechanism by which LEV could reduce epileptic seizures.
AB - Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy. Epileptic rats developed clear signs of hyperexcitability, i.e., an elevated Glu/GABA ratio in the DH. The LEV concentration in blood after 7 days of treatment was within the therapeutic range. In contrast, LEV was not detected four days after mini-pump removal (washout period). Furthermore, LEV restored the Glu/GABA ratio to approximately the control level and significantly increased the GABA concentration after the initiation of high-K+ conditions. Based on these data, LEV treatment restored the lost balance between the excitatory and inhibitory systems under basal conditions. Moreover, LEV showed a selective effect by preferentially increasing vesicular release of GABA, a mechanism by which LEV could reduce epileptic seizures.
KW - Amino acids
KW - Dorsal hippocampus
KW - Levetiracetam
KW - Microdialysis assay
KW - Temporal lobe epilepsy
UR - http://www.scopus.com/inward/record.url?scp=85044381286&partnerID=8YFLogxK
U2 - 10.1016/j.eplepsyres.2018.01.004
DO - 10.1016/j.eplepsyres.2018.01.004
M3 - Artículo
C2 - 29331845
AN - SCOPUS:85044381286
SN - 0920-1211
VL - 140
SP - 111
EP - 119
JO - Epilepsy Research
JF - Epilepsy Research
ER -