Anticonvulsant activity of calmodulin antagonist W-7 in convulsions induced by lindane and BayK-8644: effects in c-fos expression
Tusell, J.M.; Barron, S.; Serratosa, J.
Neurotoxicology 15(3): 751-756
1994
ISSN/ISBN: 0161-813X PMID: 7531829 Document Number: 832
The anticonvulsant activity of calmodulin antagonist W-7, was investigated on convulsions induced in mice by the insecticide lindane and by the calcium channel agonist Bay K-8644. We also studied the inhibitory effect of W-7 on c-fos mRNA expression induced by both convulsants. We observed a good correlation between doses and the acute convulsive effects of lindane and Bay K-8644. The incidence rate and time to onset were clearly dose-dependent. W-7 antagonized the convulsive effects of lindane and BayK-8644 in all the parameters studied. A significant decrease in the incidence rate and time to onset were observed when they are compared with the values obtained with the ED-100 of lindane and BayK-8644 induced seizures. We have compared the etiology of the induction of c-fos by lindane with that of Bay K-8644. Both were able to activate the mRNA expression of the protooncogene. The pattern of this expression displayed by in situ hybridization was very similar. A dramatic increase was found in dentate gyrus and high levels of mRNA expression also occurring in hippocampal fields and cortical regions. in accordance with the behavioural results, W-7 antagonized also the c-fos expression induced by lindane and BayK-8644. Our results suggest that lindane as BayK-8644 may activate voltage-dependent calcium channels leading to calmodulin activation.
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