ATTENUATION OF HIPPOCAMPAL LONG-TERM POTENTIATION BY ETHANOL - A PATCH-CLAMP ANALYSIS OF GLUTAMATERGIC AND GABAERGIC MECHANISMS

Long-term potentiation of synaptic transmission (LTP) of the perforant path-dentate gyrus synapse is induced by 5 Hz, theta-like stimulation patterns. Such stimuli induce plasticity that is most likely driven b y a decrease in synaptic inhibition (disinhibition) mediated by GABA. autoreceptors. In the present study, we demonstrate that LTP induced i n this manner is completely antagonized by ethanol. In order to determ ine the site of ethanol inhibition of LTP induced by theta-like stimul ation, we combined slice patch recordings with pharmacologic isolation of the individual glutamatergic and GABAergic synaptic currents. The present experiments revealed that ethanol inhibited NMDA receptor-medi ated synaptic currents without potentiation of GABA(A) currents or att enuation of GABA(B)-mediated fading of GABA(A) synaptic currents. Thes e observations with ethanol contrasted with the actions of the water-s oluble benzodiazepine midazolam, which strongly potentiated GABA(A) sy naptic currents, reversed the effect of GABA(B)-mediated fading of GAB A(A) synaptic currents, and therefore blocked the resulting NMDA synap tic currents. These data indicate that the effects of ethanol on long- term changes in synaptic strength in the rat hippocampal formation are due primarily to an action at the NMDA receptor-channel complex.