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Rats With Different Thresholds to Clonic Convulsions Induced by DMCM Differ in the Binding of [3H]-MK-801 and [3H]-Ouabain in the Membranes of Brain Regions

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Abstract

Considering the putative participation of N-methyl-D-aspartate (NMDA) receptors and the Na+, K+-ATPase enzymes in the susceptibility to convulsions induced by the benzodiazepine inverse agonist methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), the present study sought to determine if rats with high (HTR) and low (LTR) thresholds to clonic convulsions induced by DMCM differed in the following aspects: the binding of NMDA receptors by [3H]-MK-801, Na+, K+-ATPase activity (K+-stimulated p-nitrophenylphosphatase) and high-affinity [3H]-ouabain binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [3H]-MK-801 in the hippocampus, frontal cortex and striatum. The subgroups did not differ in K+-p-nitrophenylphosphatase activity, but the LTR subgroup had a lower density of isozymes with a high-affinity to ouabain in the brainstem and in the frontal cortex and a lower affinity to ouabain in the hippocampus than the HTR subgroup. These results suggest that NMDA receptors and ouabain-sensitive Na+, K+-ATPase isozymes may underlie the susceptibility to DMCM-induced convulsions.

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Acknowledgments

We thank Ricardo Marques for his technical assistance. This research was supported by Associação Fundo de Incentivo à Pesquisa (AFIP). M.B. Contó was the recipient of a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes).

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  1. Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP, 04023-062, Brazil

    Marcos Brandão Contó, José Gilberto Barbosa de Carvalho & Marco Antonio Campana Venditti

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  1. Marcos Brandão Contó
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  2. José Gilberto Barbosa de Carvalho
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Correspondence to Marcos Brandão Contó.

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Contó, M.B., de Carvalho, J.G.B. & Venditti, M.A.C. Rats With Different Thresholds to Clonic Convulsions Induced by DMCM Differ in the Binding of [3H]-MK-801 and [3H]-Ouabain in the Membranes of Brain Regions. Neurochem Res 37, 1442–1449 (2012). https://doi.org/10.1007/s11064-012-0730-4

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  • DOI: https://doi.org/10.1007/s11064-012-0730-4

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