Effects of zonisamide on c-Fos expression under conditions of tacrine-induced tremulous jaw movements in rats: a potential mechanism underlying its anti-parkinsonian tremor effect.
OBJECTIVE
To examine the mechanisms underlying the anti-tremor effect of zonisamide in rats under conditions of tacrine-induced tremulous jaw movements (TJMs).


METHODS
Male adult rats received systemic administration of either zonisamide (5 or 50mg/kg) or vehicle at 20min prior to the administration of tacrine hydrochloride (5mg/kg). Animals were sacrificed 2h later, and the brains collected and immunostained for quantitative assessment of c-Fos expression.


RESULTS
There was no effect of zonisamide on tacrine-induced c-Fos expression in the ventrolateral striatum, a primary site of the pharmacological action of tacrine. Zonisamide suppressed the tacrine-induced c-Fos expression in the cortex, the dorsal striatum, and the nucleus accumbens, which are involved in the architecture of the cortico-basal ganglia-thalamocortical circuits.


CONCLUSIONS
The anti-TJM effect of zonisamide may not relate to suppression of neural activity specifically in primary tremor-generating sites, but may be due to a more broad inhibitory effect on tremor-related structures such as the cortex or the striatum. This effect of zonisamide may be a contributing mechanism underlying its therapeutic efficacy on parkinsonian tremor.
Miwa
Hideto
H
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jp
Kubo
Tomomi
T
Suzuki
Ai
A
Kondo
Tomoyoshi
T
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D007555:Isoxazoles / Q000627:therapeutic use*; D007568:Jaw / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D016760:Proto-Oncogene Proteins c-fos; D000078305:Zonisamide; D013619:Tacrine