Rq. Hu et al., Regulation of gamma-aminobutyric acid (GABA) release in cerebral cortex inthe gamma-hydroxybutyric acid (GHB) model of absence seizures in rat, NEUROPHARM, 39(3), 2000, pp. 427-439
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 circuitr
y may play a role. In the present study,we determined the basal and K+-evok
ed release of GABA and glutamate in the superficial laminae of frontal cort
ex during GHB-induced absence seizures. Our data indicate that both the bas
al 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 app
earance and disappearance of the observed changes in basal and K+-evoked ex
tracellular levels of GABA correlated with the onset and offset of absence
seizures. In contrast, neither the basal nor the K+-evoked release of gluta
mate was altered in superficial laminae of cerebral cortex at any time duri
ng the absence seizures. Intracortical perfusion of the GABA(B) receptor an
tagonists, 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 ba
sal and depolarization-induced release of GABA in cerebral cortex, and furt
her, that this action of GHB may play a role in the mechanism by which GHB
induces absence seizures. (C) 2000 Elsevier Science Ltd. All rights reserve
d.