A Neuropharmacological Analysis of PTZ-Induced Kindling in Mice

Depto. de Farmacologia, Universidade Federal do Rio Grande do Sul, RS, Brazil.
General Pharmacology 08/1998; 31(1):47-50. DOI: 10.1016/S0306-3623(97)00423-0
Source: PubMed


1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic changes associated with epileptic features. 2. The aim of this study was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, significantly increased (169.8%) the specific binding of [3H]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ-induced kindling and that, as in rats, the kindling increases the specific [3H]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena.

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    • "Electrical kindling usually stimulates a specific brain region, such as amygdala, hippocampus or other brain regions, via chronically implanted depth electrodes (32, 142, 143). Chemical kindling, such as pentylenetetrazoleis ultilized in some studies, but this method has been much less utilized than electrical kindling (144, 145). Pentylenetetrazole kindling involves repeated injection of pentylenetetrazole to cause gradual seizure development as a result of which a significant neuronal loss in hippocampus CA1 and CA3 structures have been observed (144). "
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    • "During the behavioral assessment, the following parameters were registered: latency to the first seizure severity score III, duration of the first seizure severity score III (both in seconds), and the number of seizures. Additionally, convulsive behavior was rated according to the following scale (adapted from Da Silva et al., 1998): 0 = no convulsive behavior; I = jerks of short duration; II = clonic forelimb convulsions lasting less than 3 s; III = clonic forelimb convulsions lasting more than 3 s; IV = generalized convulsions with tonic extension episodes and full status epilepticus; V = death. In the present study, we used in behavioral and biochemical assays only those animals which presented seizures at a severity score rate ≥ III. "
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    ABSTRACT: Neuropeptide S (NPS) and its receptor were recently discovered in the central nervous system. In rodents, NPS promotes hyperlocomotion, wakefulness, anxiolysis, anorexia, and analgesia and enhances memory when injected intracerebroventricularly (i.c.v.). Herein, NPS at different doses (0.01, 0.1 and 1nmol) was i.c.v. administered in mice challenged with pentylenetetrazole (PTZ; 60mg/kg) repeatedly injected. Aiming to assess behavioral alterations and oxidative damage to macromolecules in the brain, NPS was injected 5min prior to the last dose of PTZ. The administration of NPS only at 1nmol increased the duration of seizures evoked by PTZ, without modifying frequency and latency of seizures. Biochemical analysis revealed that NPS attenuated PTZ-induced oxidative damage to proteins and lipids in the hippocampus and cerebral cortex. In contrast, the administration of NPS to PTZ-treated mice increased DNA damage in the hippocampus, but not cerebral cortex. In conclusion, this is the first evidence of the potential proconvulsive effects of NPS in mice. The protective effects of NPS against lipid and protein oxidative damage in the mouse hippocampus and cerebral cortex evoked by PTZ-induced seizures are quite unexpected. The present findings were discussed analyzing the paradoxical effects of NPS: facilitation of convulsive behavior and protection against oxidative damage to lipids and proteins.
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    • "The development of chemical kindling induces permanent changes in mouse brain (Ekonomou et al., 2001; da Silva et al., 1998; De Luca et al., 2005). The amino acid level modifications in brain during seizure itself could result from both the kindling process and the physiological shock induced by the seizure. "
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