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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.

Author(s): Miwa H, Kubo T, Suzuki A, Kondo T

Affiliation(s): Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jp

Publication date & source: 2009-01, Parkinsonism Relat Disord., 15(1):30-5. Epub 2008 Aug 8.

Publication type: Research Support, Non-U.S. Gov't

OBJECTIVES: 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. CONCLUSION: 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.

Page last updated: 2009-10-20

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