The usefulness of olfactory bulb kindling as a model for evaluation of antiepileptics.
OBJECTIVE
The present study was undertaken to clarify the behavioral and electroencephalographic characteristics of olfactory bulb (OB) kindling in rats, in comparison with those of amygdala (AMG) kindling. In addition, the usefulness of OB kindling as a model to evaluate antiepileptics was studied.


METHODS
Bipolar electrical stimulation was applied to the OB or AMG every day until generalized seizure was achieved. Antiepileptics (carbamazepine, sodium valproate, zonisamide, clobazam, and topiramate), which are used for complex partial epilepsy or secondary generalized epilepsy in clinical practice, were orally administrated to kindled rats.


RESULTS
The afterdischarge (AD) threshold of OB kindling is not different from that of AMG kindling. OB-kindled rats showed more rapid development of the seizure stage and AD duration than AMG-kindled rats; however, fully kindled AD duration did not differ between groups. In AMG kindled rats, AD on day 1 was localized only at the stimulation site, whereas in OB-kindled rats, AD on day 1 was observed at not only the stimulation site (OB) but also in the frontal cortex, hippocampus, and AMG. All five antiepileptics significantly inhibited both the seizure stage and AD duration in OB-kindled rats. In addition, carbamazepine, zonisamide, and topiramate were more effective in suppressing OB-kindled seizures. Zonisamide was not effective at any dose tested in AMG-kindled rats.


CONCLUSIONS
OB kindling can be used as a new valuable model to evaluate antiepileptic drugs, with the advantage of its rapid development and the efficacy of antiepileptics.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Akinori
A
Fujiwara
Yusuke
Y
Watanabe
Kenshi
K
Takechi
Takashi
T
Ishikawa
Yuko
Y
Kaida
Masaaki
M
Akagi
Chiaki
C
Kamei
D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology; D002220:Carbamazepine / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D017029:Epilepsy, Complex Partial / Q000503:physiopathology / Q000517:prevention & control; D004829:Epilepsy, Generalized / Q000503:physiopathology / Q000517:prevention & control; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007555:Isoxazoles / Q000494:pharmacology; D007696:Kindling, Neurologic; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D014635:Valproic Acid / Q000494:pharmacology; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide; D014635:Valproic Acid