The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a field potential analysis.
The mechanism of action of the recently developed anticonvulsant gabapentin (GBP) used for treatment of partial seizures [12] is largely unknown. Rat hippocampal slices were maintained in vitro and the effects of microapplication of nipecotic acid (NPA), which promotes the release and blocks uptake of GABA, on the synaptically-evoked population excitatory postsynaptic potential (EPSP) were assessed before and after 1 h bath application of GBP. GBP treatment did not alter the population EPSP amplitude to paired or multiple stimuli, but nearly doubled the shunting effects of NPA on the EPSP with no effect on the presynaptic volley. The NPA-induced shunting of the EPSP was bicuculline-sensitive, indicating its mediation by GABAA receptor activation. These results suggest that GBP may increase free GABA levels in hippocampal cells, the release of which may be enhanced under conditions of promoted GABA release. Moreover, the study presents a methodology to electrophysiologically assess relative free GABA levels using field potential analysis in the adult rat brain.
Honmou
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O
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Oyelese
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AA
Kocsis
J D
JD
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009557:Nipecotic Acids / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D009557:Nipecotic Acids; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D011392:Proline; C010983:homoproline