Effects of levetiracetam on hippocampal kindling in Noda epileptic rats.
In order to clarify the seizure susceptibility of Noda epileptic rat (NER) and the antiepileptic effects of levetiracetam (LEV), we performed electrical hippocampal kindling in NERs compared with Wistar rats (experiment 1), and hippocampal kindling in NERs with LEV administration (experiment 2). In experiment 1, electrical stimulation was administered to the right dorsal hippocampus of NERs and Wistar rats once per day. In experiment 2, NERs were randomly assigned to group L (LEV administration) and C (saline administration). Following daily administration of LEV (240 mg/kg, i.p.) to group L and saline to group C, hippocampal kindling was performed from the 5th day of consecutive LEV or saline administration. As a result of experiment 1, all NERs exhibited stage 5 (falling) or stage 6 seizure (running/jumping, subsequent seizure) from the first electrical stimulation. In experiment 2, LEV suppressed development of hippocampal kindling, increased the afterdischarge threshold of the hippocampus and inhibited stage 6 seizures in NER. Although LEV prolonged the afterdischarge duration at the first stage 5 seizure significantly, there was a tendency to prolong the latency to generalization by LEV. These findings indicate that NER is susceptible not only to limbic seizures but also to brainstem seizures. Furthermore, LEV may have inhibitory effects not only on the hippocampus but also on other neuronal pathways to secondary generalization in this rat model.
Ishimaru
Yuji
Y
Department of Psychiatry and Neurology, Asahikawa Medical College, Midorigaoka-higashi 2-1-1-1, Asahikawa, Japan. ishimaru@asahikawa-med.ac.jp
Chiba
Shigeru
S
Serikawa
Tadao
T
Sasa
Masashi
M
Inaba
Hiroko
H
Tamura
Yoshiyuki
Y
Ishimoto
Takahiro
T
Takasaki
Hideki
H
Sakamoto
Kazutaka
K
Yamaguchi
Kazuhide
K
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000235:genetics; D000077287:Levetiracetam; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam