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Zimelidine decreases seizure susceptibility in stressed mice

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Summary.

To further evaluate whether selective serotonin reuptake inhibitors (SSRIs) have pro- or anticonvulsant properties and whether these properties will be modified by stress, we studied the effect of zimelidine on the convulsions produced by picrotoxin, a GABAA receptor antagonist, in unstressed and swim stressed mice. Zimelidine potentiated the ability of swim stress to enhance the threshold doses of intravenously administered picrotoxin producing convulsant signs and death, without having an effect in unstressed mice. The anticonvulsant effect of zimelidine was counteracted with mianserin, the antagonist of 5-HT2A/2C, and diminished with WAY-100635, a selective antagonist of 5-HT1A receptors. In stressed mice, WAY-100635 prevented the anticonvulsant effect of 8-OH-DPAT, a 5-HT1A receptor agonist. SB-269970 and ketanserin, the antagonists of 5-HT7 and 5-HT2A receptors, respectively, failed to reduce the effect of zimelidine. The results suggest the involvement of 5-HT2C and 5-HT1A receptors in the anticonvulsant effects of zimelidine and possibly other SSRIs in stress.

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  1. Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruder Bošković Institute, Zagreb, Croatia

    D. Peričić, D. Š. Štrac & J. Vlainić

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Peričić, D., Štrac, D. & Vlainić, J. Zimelidine decreases seizure susceptibility in stressed mice. J Neural Transm 113, 1863–1871 (2006). https://doi.org/10.1007/s00702-006-0489-3

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