Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence-like seizures induced by GHB. 1995

P K Banerjee, and O C Snead
Department of Neurology, University of Southern California School of Medicine, Los Angeles, USA.

The ventrobasal nucleus of thalamus (VB) is considered to be intimately involved in the genesis of experimental absence-like seizures. Bilateral microinfusion of gamma-hydroxybutyric acid (GHB) into VB or systemic administration of gamma-butyrolactone, the pro-drug of GHB, induces generalized absence-like seizures in rats. In the present study, the basal and K(+)-evoked extracellular output of endogenous gamma-aminobutyric acid (GABA) and glutamate (GLU) in behaving rat VB nucleus was characterized 1) during unilateral GHB perfusion into VB and 2) during the course of generalized absence-like seizures induced by GHB. Although the basal extracellular release of GABA was inhibited by GHB (250-1500 microM) in a concentration-dependent manner, basal GLU levels remained unaltered. However, K(+)-evoked release of both GABA and GLU was significantly attenuated by GHB. During GHB-induced absence-like seizures, a similar decrease in basal GABA or K(+)-evoked GABA and GLU levels was observed. These effects of GHB were partially reversed by the specific GHB receptor antagonist NCS 382. (-)-Baclofen (10-50 microM) also produced a concentration-dependent decrease in basal and K(+)-evoked levels of GABA and GLU in this thalamic nucleus. The effects of either (-)-baclofen or GHB on the release of GABA and GLU were selectively antagonized by the GABAB receptor antagonists phaclofen (0.75-2 mM) and CGP 35348 (50-200 microM), respectively. These results suggest that by selectively modulating the basal and K(+)-evoked release of GABA and GLU, GHB induces, in the thalamic ventrobasal relay nucleus, an optimal "excitatory" environment conducive to the generation of absence seizures. Moreover, the data raise the possibility that a presynaptic GHB/GABAB receptor complex occurs in VB.

UI MeSH Term Description Entries
D008297 Male Males
D009943 Organophosphorus Compounds Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS. Organophosphorus Compound,Organopyrophosphorus Compound,Organopyrophosphorus Compounds,Compound, Organophosphorus,Compound, Organopyrophosphorus,Compounds, Organophosphorus,Compounds, Organopyrophosphorus
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
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
D005110 Extracellular Space Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall. Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
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
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D001418 Baclofen A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. Baclophen,Chlorophenyl GABA,Apo-Baclofen,Atrofen,Ba-34,647,Ba-34647,Baclofen AWD,Baclofène-Irex,Baclospas,CIBA-34,647-BA,Clofen,Gen-Baclofen,Genpharm,Lebic,Lioresal,Liorésal,Nu-Baclo,PCP-GABA,PMS-Baclofen,beta-(Aminomethyl)-4-chlorobenzenepropanoic Acid,beta-(p-Chlorophenyl)-gamma-aminobutyric Acid,AWD, Baclofen,Apo Baclofen,ApoBaclofen,Ba34,647,Ba34647,Baclofène Irex,BaclofèneIrex,CIBA34,647BA,GABA, Chlorophenyl,Gen Baclofen,GenBaclofen,Nu Baclo,NuBaclo,PMS Baclofen,PMSBaclofen

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