ACUTE EFFECTS OF GAMMA-VINYL GABA(VIGABATRIN) ON HIPPOCAMPAL GABAERGIC INHIBITION IN-VITRO

The acute effects of gamma-vinyl-GABA (GVG) on GABAergic inhibition we re investigated in the hippocampal slice preparation using the paired- pulse test of inhibition during extracellular recordings. Superfusion of GVG (100-500 mu M) for 60 min resulted in a concentration-dependent decrease in GABAergic inhibition. Slices superfused with higher conce ntrations of GVG (0.5-1 mM) were hyperexcitable as demonstrated by the appearance of multiple spikes. Binding studies showed that GVG (1 mM) had no effect on the binding of [H-3]flunitrazepam or [H-3]TBOB and d isplaced no more than 15% of specific [H-3]GABA binding, which indicat es that GVG-induced disinhibition is not mediated through an action at the GABA(A) receptor complex. Consistent with this suggestion is the finding that GVG (500 mu M) had little effect on the inhibition of the orthodromically evoked CA1 population spike produced by the GABA(A) r eceptor agonist muscimol (10 mu M), whereas this inhibition was consid erably attenuated by the GABA(A) receptor antagonist, bicuculline meth iodide (5 mu M). The results of this study suggest that the acute acti ons of GVG on the GABAergic neurotransmitter system are not involved i n its anticonvulsant effect.