Abstract
SummaryWe have shown that a number of anticonvulsant drugs can reduce glutamate release at synapses in the rat entorhinal cortex (EC) in vitro. We have also shown that presynaptic NMDA receptors (NMDAr) tonically facilitate glutamate release at these synapses. In the present study we determined whether, phenytoin, gabapentin and felbamate may reduce glutamate release by blocking the presynaptic NMDAr. Whole cell patch clamp recordings of spontaneous excitatory postsynaptic currents (sEPSCs) were used as a monitor of presynaptic glutamate release. Postsynaptic NMDAr were blocked with internal dialysis with an NMDAr channel blocker. The antagonist, 2-AP5, reduced the frequency of sEPSCs by blocking the presynaptic facilitatory NMDAr, but did not occlude a reduction in sEPSC frequency by gabapentin or phenytoin. Felbamate also reduced sEPSC frequency, but this effect was occluded by prior application of 2-AP5. Thus, whilst all three drugs can reduce glutamate release, only the action of felbamate seems to be due to interaction with presynaptic NMDAr.
Highlights
Experiments in this laboratory have shown that the anticonvulsant drugs phenytoin, lamotrigine, gabapentin, pregabalin and valproate can reduce the spontaneous release of glutamate from excitatory terminals in the rat entorhinal cortex (EC) in vitro (Cunningham and Jones, 2000; Cunningham et al, 2000; 2003; 2004)
We have shown that a number of anticonvulsant drugs can reduce glutamate release at synapses in the rat entorhinal cortex (EC) in vitro
We have shown that presynaptic NMDA receptors (NMDAr) tonically facilitate glutamate release at these synapses
Summary
Experiments in this laboratory have shown that the anticonvulsant drugs phenytoin, lamotrigine, gabapentin, pregabalin and valproate can reduce the spontaneous release of glutamate from excitatory terminals in the rat entorhinal cortex (EC) in vitro (Cunningham and Jones, 2000; Cunningham et al, 2000; 2003; 2004). The effect of valproate alone appeared to depend on blockade of voltage-gated sodium channels (VGSC; Cunningham et al, 2003), whereas the reduction in release elicited by the others drugs was independent of any action on sodium channels. Pregabilin has been suggested to reduce GABA and, possibly, glutamate release in hippocampal cultures via an interaction with presynaptic NMDAr (Micheva et al, 2006).
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