Regulation of gamma-aminobutyric acid (GABA) release in cerebral cortex in the gamma-hydroxybutyric acid (GHB) model of absence seizures in rat.
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.
Hu
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RQ
Department of Pediatrics, Faculty of Medicine, Hospital for Sick Children, University of Toronto, Ontario, Canada. ruo.hu@sickkids.on.ca
Banerjee
P K
PK
Snead
O C
OC
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000493:pharmacokinetics*; D006885:Hydroxybutyrates / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D012997:Solvents / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
D018756:GABA Antagonists; D006885:Hydroxybutyrates; D018080:Receptors, GABA-B; D012997:Solvents; C111420:4-hydroxybutyric acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D015107:4-Butyrolactone