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Psychopharmacology

, Volume 126, Issue 1, pp 85–90 | Cite as

Behavioural and anticonvulsant effects of Ca2+ channel toxins in DBA/2 mice

  • H. C. Jackson
  • M. A. Scheideler
Original Investigation

Abstract

This study investigated the behavioural and anticonvulsant effects of voltage-sensitive calcium channel blockers in DBA/2 mice.ω-Conotoxin MVIIC (0.1, 0.3 μg ICV/mouse) andω-agatoxin IVA (0.1, 0.3, 1 μg ICV), which act predominantly at P- and/or Q-type calcium channels, prevented clonic and tonic sound-induced seizures in this animal model of reflex epilepsy (ED50 values with 95% confidence limits for protection against clonic sound-induced seizures were 0.09 (0.04–0.36) μg ICV and 0.09 (0.05–0.15) μg ICV, respectively and against tonic seizures 0.07 (0.03–0.16) μg ICV and 0.08 (0.04–0.13) μg ICV, respectively). The N-type calcium channel antagonistsω-conotoxin GVIA andω-conotoxin MVIIA were also tested in this model.ω-Conotoxin GVIA was anticonvulsant in DBA/2 mice, but only at high doses (3 μg ICV prevented tonic seizures in 60% of the animals; 10 μg ICV prevented clonic seizures in 60% and tonic seizures in 90% of the animals), whereasω-conotoxin MVIIA did not inhibit sound-induced seizures in doses up to 10 μg ICV. Bothω-conotoxin GVIA andω-conotoxin MVIIA induced an intense shaking syndrome in doses as low as 0.1 μg ICV, whereasω-conotoxin MVIIC andω-agatoxin IVA did not produce shaking at any of the doses examined. Finally,α-conotoxin GI (0.01–1 μg ICV) andα-conotoxin SI (0.3–30 μg ICV), which both act at acetylcholine nicotinic receptors, were not anticonvulsant and did not induce shaking in DBA/2 mice. These results confirm that blockers of N- and P-/Q-type calcium channels produce different behavioural responses in animals. The anticonvulsant effects ofω-conotoxin MVIIC andω-agatoxin IVA in DBA/2 mice are consistent with reports that P- and/or Q-type calcium channel blockers inhibit the release of excitatory amino acids and are worthy of further exploration.

Key words

ω-Conotoxins ω-Agatoxin Voltage-sensitive calcium channels (VSCC) Seizures Shaking behaviour DBA/2 mice 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. C. Jackson
    • 1
  • M. A. Scheideler
    • 1
  1. 1.Health Care Discovery, Novo Nordisk A/SMåløvDenmark

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