THE ANTICONVULSANT GABAPENTIN ENHANCES PROMOTED RELEASE OF GABA IN HIPPOCAMPUS - A FIELD POTENTIAL ANALYSIS

The mechanism of action of the recently developed anticonvulsant gabap entin (GBP) used for treatment of partial seizures [12] is largely unk nown. Rat hippocampal slices were maintained in vitro and the effects of microapplication of nipecotic acid (NPA), which promotes the releas e and blocks uptake of GABA, on the synaptically-evoked population exc itatory 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 GABA(A) receptor activation. These resul ts suggest that GBP may increase free GABA levels in hippocampal cells , the release of which may be enhanced under conditions of promoted GA BA release. Moreover, the study presents a methodology to electrophysi ologically assess relative free GABA levels using field potential anal ysis in the adult rat brain.