Zonisamide at clinically relevant concentrations inhibits field EPSP but not presynaptic fiber volley in rat frontal cortex.
We investigated the effect of Zonisamide (ZNS), a newer anti-epileptic drug, on field potentials and neuropropagation in rat frontal cortex, with the aid of the 64-channel multi-electrode dish (MED64) system. The amplitude and propagation of field potentials were expressed dimensionally in the MED64 system. ZNS (3-100 microM) inhibited the amplitude and propagation of field excitatory postsynaptic potentials (fEPSP) in a concentration dependent manner. In contrast, ZNS could not suppress the amplitude and propagation of the presynaptic fiber volley (PrV) at clinically relevant concentrations (10-30 microM). Stimulating dependency with reduction fEPSP was seen in the presence of ZNS at clinically relevant concentrations, but not with PrV. The reduction of fEPSP amplitude was not accompanied by a change in paired-pulse facilitation. These data suggest that at clinically relevant concentrations of ZNS, the suppression of neuronal propagation is at least partially due to the postsynaptic mechanism, probably through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
Huang
Chin-Wei
CW
Department of Neurology, Institute of Clinical Medicine, National Cheng-Kung University Medical Center, No. 1, University Road, Tainan, Taiwan. huangcw@mail.ncku.edu.tw
Ueno
Shinya
S
Okada
Motohiro
M
Kaneko
Sunao
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide; D010672:Phenytoin