Regulation of gamma-aminobutyric acid (GABA) release in cerebral cortex in the gamma-hydroxybutyric acid (GHB) model of absence seizures in rat. 2000

R Q Hu, and P K Banerjee, and O C Snead
Department of Pediatrics, Faculty of Medicine, Hospital for Sick Children, University of Toronto, Ontario, Canada. ruo.hu@sickkids.on.ca

Gamma-hydroxybutyric acid (GHB) has the ability to induce absence seizures. The precise way in which GHB causes seizures remains unclear, but GABA(B)- and/or GHB-mediated presynaptic mechanisms within thalamocortical circuitry may play a role. In the present study, we determined the basal and K+-evoked release of GABA and glutamate in the superficial laminae of frontal cortex during GHB-induced absence seizures. Our data indicate that both the basal and K+-evoked release of GABA were significantly decreased in laminae I-III of frontal cortex at the onset of GHB-induced absence seizures. The appearance and disappearance of the observed changes in basal and K+-evoked extracellular levels of GABA correlated with the onset and offset of absence seizures. In contrast, neither the basal nor the K+-evoked release of glutamate was altered in superficial laminae of cerebral cortex at any time during the absence seizures. Intracortical perfusion of the GABA(B) receptor antagonists, CGP 35348 and phaclofen as well as the GHB receptor antagonist, NCS 382 attenuated GHB-mediated changes in the basal and K+-evoked release of GABA. These data suggest that GHB induces a selective decrease in the basal and depolarization-induced release of GABA in cerebral cortex, and further, that this action of GHB may play a role in the mechanism by which GHB induces absence seizures.

UI MeSH Term Description Entries
D008297 Male Males
D011189 Potassium Chloride A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA. Slow-K,Chloride, Potassium
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
D004832 Epilepsy, Absence A seizure disorder usually occurring in childhood characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736) Akinetic Petit Mal,Epilepsy, Minor,Petit Mal Epilepsy,Pyknolepsy,Absence Seizure Disorder,Childhood Absence Epilepsy,Epilepsy Juvenile Absence,Epilepsy, Absence, Atypical,Epilepsy, Petit Mal,Juvenile Absence Epilepsy,Pykno-Epilepsy,Seizure Disorder, Absence,Absence Epilepsy,Absence Epilepsy, Childhood,Absence Epilepsy, Juvenile,Absence Seizure Disorders,Epilepsy, Childhood Absence,Epilepsy, Juvenile Absence,Minor Epilepsy,Petit Mal, Akinetic,Pykno Epilepsy,Pyknolepsies,Seizure Disorders, Absence
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D006885 Hydroxybutyrates Salts and esters of hydroxybutyric acid. Hydroxybutyric Acid Derivatives,Hydroxybutyric Acids,Acid Derivatives, Hydroxybutyric
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
D012997 Solvents Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed) Solvent
D013788 Thalamus Paired bodies containing mostly GRAY MATTER and forming part of the lateral wall of the THIRD VENTRICLE of the brain. Thalamencephalon,Thalamencephalons

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