Topiramate-antagonism of L-glutamate-induced paroxysms in planarians - PubMed (original) (raw)

Topiramate-antagonism of L-glutamate-induced paroxysms in planarians

Robert B Raffa et al. Eur J Pharmacol. 2010.

Abstract

We recently reported that NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induce concentration-dependent paroxysms in planarians (Dugesia dorotocephala). Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. We demonstrate that: (1) L-glutamate (1-10 mM), but not D-glutamate, induced dose-related paroxysms, and that (2) topiramate dose-relatedly (0.3-3 mM) inhibited L-glutamate-induced paroxysms. These results provide further evidence of a topiramate-sensitive glutamate receptor-mediated activity in this model.

Copyright © 2010 Elsevier B.V. All rights reserved.

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Figures

Fig 1

Fig 1

Representative photographs of the spontaneous locomotor activity displayed by planarians tested in water. When quantified as rate of gridlines crossed, locomotor activity is nearly linear for at least 10 minutes (see refs in Raffa and Rawls, 2008).

Fig 2

Fig 2

Representative photographs of paroxysms displayed when planarians were tested in L-glutamate. The behavior consisted of spasmodic twisting and contracture in-place, with loss of forward movement.

Fig 3

Fig 3

L-glutamate (filled circles), but not D-glutamate (filled square), induced concentration-related paroxysms, expressed as the mean (± S.E.M.) over a 5-min observation period. N = 8 planarians per group.

Fig 4

Fig 4

Topiramate (0.3, 1, 3 mM) attenuated the paroxysms induced by a fixed concentration of L-glutamate (3 mM). N = 8 planarians per group.

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