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

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 50 mg/kg) or vehicle at 20 min prior to the administration of tacrine hydrochloride (5 mg/kg). Animals were sacrificed 2 h 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. (C) 2008 Published by Elsevier Ltd.