Effects of postsynaptic GABA(B) receptor activation on epileptiform activity in hippocampal slices.
GABA(B) receptor agonists have been reported to have both pro- and antiepileptic properties. Here, the effects of a GABA(B) receptor agonist, baclofen, were studied on epileptiform activity induced in the absence of synaptic transmission - to focus on the postsynaptic effects. Perfusion of hippocampal slices with 0-added calcium and high potassium induced field bursts in CA1 and the dentate gyrus. Addition of baclofen caused a transient suppression of the field bursts in CA1 and the dentate gyrus. The duration of the suppression was dependent on the concentration of baclofen and when the bursts reappeared they had a larger amplitude than before baclofen. Baclofen also suppressed the multiple population spikes evoked by antidromic stimulation in the dentate gyrus. This effect also decreased with continued baclofen perfusion. The effects of baclofen on the amplitude of the spontaneous field bursts and on the stimulation-induced multiple population spikes were blocked by the GABA(B) receptor antagonist SCH 50911, suggesting that these effects of baclofen are mediated by GABA(B) receptor activation. Baclofen significantly increased the peak extracellular K(+) concentration during each field burst in the dentate gyrus but did not change the baseline level of K(+) between field bursts. The results suggest that postsynaptic GABA(B) receptor activation by baclofen has transient antiepileptic effects followed by a rebound increase in excitability.
Xiong
Z Q
ZQ
Department of Pharmacology and Division of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Stringer
J L
JL
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D019204:GTP-Binding Proteins; D001418:Baclofen; D000241:Adenosine; D011188:Potassium