EFFECT OF A GAMMA-AMINOBUTYRIC-ACID UPTAKE INHIBITOR, NNC-711, ON SPONTANEOUS POSTSYNAPTIC CURRENTS IN CULTURED RAT HIPPOCAMPAL-NEURONS - IMPLICATIONS FOR ANTIEPILEPTIC DRUG DEVELOPMENT

The effect of a novel gamma-aminobutyric acid (GABA) uptake inhibitor, NNC-711, on spontaneous postsynaptic currents was studied in cultured rat hippocampal neurons by the whole cell patch clamp method. NNC-711 decreased the amplitude of inhibitory postsynaptic currents (IPSCs) a nd did not prolong the decay. NNC-711 also decreased the amplitude of excitatory PSCs (EPSCs). The GABA(B) receptor antagonist 2-OH saclofen abolished the effect on both IPSCs and EPSCs. NNC-711 itself induced no current and had no effect on currents induced by exogenously applie d GABA. These findings suggest that duration of GABA(A)-receptor media ted IPSCs is not determined by GABA uptake and that GABA uptake inhibi tors may work by allowing GABA to remain in the synaptic area long eno ugh to activate presynaptic GABA(B) receptors.