LOW ETHANOL CONCENTRATIONS ENHANCE GABAERGIC INHIBITORY POSTSYNAPTIC POTENTIALS IN HIPPOCAMPAL PYRAMIDAL NEURONS ONLY AFTER BLOCK OF GABA(B) RECEPTORS

Despite considerable evidence that ethanol can enhance chloride flux t hrough the gamma-aminobutyric acid type A (GABA(A)) receptor-channel c omplex in several central neuron types, the effect of ethanol on hippo campal GABAergic systems Is still controversial. Therefore, we have re evaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolati on of the various components of excitatory and inhibitory synaptic pot entials, using intracellular current- and voltage-clamp recording meth ods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynap tic potentials/currents (IPSP/Cs) containing both GABA(A) and GABA(B) components. However, after selective pharmacological blockade of the G ABA(B) component of the IPSP (GABA(B)-IPSP/C) by CGP-35348, low concen trations of ethanol (22-66 mM) markedly enhanced the peak amplitude, a nd especially the area, of the GABA(A) component (GABA(A)-IPSP/C) in m ost CA1 pyramidal neurons. Ethanol had no significant effect on the pe ak amplitude or area of the pharmacologically isolated GABA(B)-inhibit ory postsynaptic current (IPSC). These results provide new data showin g that activation of GABA(B) receptors can obscure ethanol enhancement of GABA(A) receptor function in hippocampus and suggest that similar methods of pharmacological isolation might be applied to other brain r egions showing negative or mixed ethanol-GABA interactions.