Biphasic action of vigabatrin on cortical epileptic after-discharges in rats. 2004

Pavel Mares, and Romana Slamberová
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. maresp@biomed.cas.cz

The time course of the anticonvulsant effect of vigabatrin against cortically induced epileptic after-discharges (ADs) was studied in freely moving rats with implanted electrodes. Adult rats (n=30) were exposed to five stimulation sessions each consisting of six stimulation series at 20-min intervals. The first session was a control one, then two groups of animals (n=10 each) were given vigabatrin (600 or 1,200 mg/kg i.p.), the control animals received physiological saline. Stimulation sessions were repeated 1, 24, 48, and 96 hours after the injection. Control animals exhibited an increased transition from the spike-and-wave type of AD to the second, "limbic" type and an increased intensity of movements accompanying stimulation. ADs in the second and subsequent sessions were, however, shorter than in the first session. Vigabatrin facilitated the transition to the second type of AD 1 h after administration but suppressed this transition as well as decreased the number of stimulations eliciting ADs 48 h later. AD duration and the severity of clonic seizures accompanying spike-and-wave ADs were influenced similarly. The effects of the lower dose of vigabatrin were more marked than those of the higher dose. The biphasic action of vigabatrin in our model might be due either to uneven changes of GABA concentration in different brain structures or to an additional mechanism of action. Our results in a cortical model of seizure demonstrate that the sequence of pro- and anticonvulsant actions of vigabatrin is not restricted to seizures of limbic origin and might represent a general phenomenon.

UI MeSH Term Description Entries
D008297 Male Males
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D020888 Vigabatrin An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID and is used as an anticonvulsant. (From Martindale The Extra Pharmacopoeia, 31st ed) gamma-Vinyl-gamma-Aminobutyric Acid,Sabril,Sabrilex,gamma-Vinyl-GABA,gamma Vinyl GABA,gamma Vinyl gamma Aminobutyric Acid

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