Navegando por Palavras-chave "DMCM"

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    Behavioral differences between subgroups of rats with high and low threshold to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist
    (Elsevier B.V., 2005-11-01) Contó, Marcos Brandão [UNIFESP]; Carvalho, JGB de; Venditti, Marco Antonio Campana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    In epileptic patients, there is a high incidence of psychiatric comorbidities, such as anxiety. Gamma-aminobutyric acid (GABA) ionotropic receptor GABA(A)/benzodiazepine allosteric site is involved in both epilepsy and anxiety. This involvement is based on the fact that benzodiazepine allosteric site agonists are anticonvulsant and anxiolytic drugs; on the other hand, benzodiazepine inverse agonists are potent convulsant and anxiogenic drugs. the aim of this work was to determine if subgroups of rats selected according to their susceptibility to clonic convulsions induced by a convulsant dose 50% (CD50) of DMCM, a benzodiazepine inverse agonist, would differ in behavioral tests commonly used to measure anxiety (elevated plus-maze, open field) and depression (forced swimming test). in the first experiment, subgroups of adult male Wistar rats were selected after a single dose of DMCM and in the second experiment they were selected after two injections of DMCM given after an interval of 1 week. Those rats presenting full clonic convulsions were termed Low Threshold rats to DMCM-induced clonic convulsions (LTR) and those not having clonic convulsions High Threshold rats to DMCM-induced clonic convulsions (HTR). in both experiments, only those rats presenting full clonic convulsions induced by DMCM and those not showing any signs of motor disturbances were used in the behavioral tests. the results showed that the LTR subgroup selected after two injections of a CD50 of DMCM spent a significantly lower time in the open arms of the elevated plus-maze and in the off the walls area of the open field; moreover, this group also presented a higher number of rearings in the open field. There were no significant differences between HTR and LTR subgroups in the forced swimming test. LTR and HTR subgroups selected after only one injection of DMCM did not differ in the three behavioral tests. To verify if the behavioral differences between HTR and LTR subgroups of rats selected after two injections of DMCM were due to the clonic convulsion, another experiment was carried out in which subgroups of rats susceptible and nonsusceptible to clonic convulsions induced by a CD50 of picrotoxin, a GABA(A) receptor channel blocker, were selected and submitted to the elevated plus-maze and open field tests. the results obtained did not show any significant differences between these two subgroups in the elevated plus-maze and open field tests. in another approach to determine the relation between fear/anxiety and susceptibility to clonic convulsions, subgroups of rats were selected in the elevated plus-maze as more or less fearful/anxious. the CD50 for clonic convulsions induced by DMCM was determined for each of these two subgroups. the results showed a significantly lower CD50 for the more fearful/anxious subgroup, which means a higher susceptibility to clonic convulsions induced by DMCM. the present findings show a relation between susceptibility to clonic convulsions and fear/anxiety and vice versa which may be due to differences in the assembly of GABA(A)/allosteric benzodiazepine site receptors in regions of the brain. (c) 2005 Elsevier Inc. All rights reserved.
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    Rats with different thresholds for DMCM-induced clonic convulsions differ in the sleep-time of diazepam and [H-3]-Ro 15-4513 binding
    (Elsevier B.V., 2012-02-01) Contó, Marcos Brandão [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; Barbosa de Carvalho, Jose Gilberto [UNIFESP]; Venditti, Marco Antonio Campana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The current study investigated the possible inherent relationship between convulsions and sleep involving the GABA(A)/benzodiazepine site complex. the aim of this study was to determine if rats with high (HTR) and low (LTR) thresholds for clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ in the following aspects: (1) sensitivity to the hypnotic effects of the GABA(A) positive allosteric modulators diazepam, pentobarbital and ethanol and (2) in the binding of [H-3]-flunitrazepam, a benzodiazepine agonist, measured by autoradiography, and [H-3]-Ro 15-4513, a benzodiazepine partial inverse agonist, to membranes from discrete brain regions. the LTR subgroup presented a shorter diazepam-induced sleeping time compared to that of the HTR subgroup. Biochemical assays revealed that the LTR subgroup did not differ in [H-3]-flunitrazepam binding compared to the HTR subgroup. With respect to the binding of [H-3]-Ro 15-4513, the LTR subgroup had higher binding in the brainstem and lower binding in the striatum compared to the HTR subgroup. These results suggest that differences in the benzodiazepine site on the GABA(A) receptor may underlie the susceptibility to DMCM-induced convulsions and sensitivity to the hypnotic effect of diazepam. (C) 2011 Elsevier B.V. All rights reserved.
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    Rats With Different Thresholds to Clonic Convulsions Induced by DMCM Differ in the Binding of [H-3]-MK-801 and [H-3]-Ouabain in the Membranes of Brain Regions
    (Springer, 2012-07-01) Contó, Marcos Brandão [UNIFESP]; Barbosa de Carvalho, Jose Gilberto [UNIFESP]; Venditti, Marco Antonio Campana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    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-beta-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 [H-3]-MK-801, Na+, K+-ATPase activity (K+-stimulated p-nitrophenylphosphatase) and high-affinity [H-3]-ouabain binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [H-3]-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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    Relationship between thresholds to convulsions induced by a benzodiazepine inverse agonist and [H-3]-L-glutamate binding in the membranes of brain regions
    (Springer, 2013-04-01) Contó, Marcos Brandão [UNIFESP]; Barbosa de Carvalho, Jose Gilberto [UNIFESP]; Venditti, Marco Antonio Campana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Although some studies have investigated the influence of kindling model of epilepsy on the glutamatergic neurotransmission, the relation between glutamatergic receptors and seizure susceptibility remains unclear. the present study sought to determine if rats with high (HTR) and low (LTR) thresholds to clonic convulsions induced by the benzodiazepine inverse agonist DMCM differed in the [H-3]-l-glutamate binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [H-3]-l-glutamate in the hippocampus, frontal cortex and amygdala plus limbic cortex, suggesting that glutamatergic receptors in these brain regions may underlie the susceptibility to DMCM-induced convulsions.