TY - JOUR T1 - Differential GABA<sub>B</sub> Receptor Modulation of Ethanol Effects on GABA<sub>A</sub> Synaptic Activity in Hippocampal CA1 Neurons JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1082 LP - 1089 DO - 10.1124/jpet.104.075663 VL - 312 IS - 3 AU - Peter H. Wu AU - Wolfgang Poelchen AU - William R. Proctor Y1 - 2005/03/01 UR - http://jpet.aspetjournals.org/content/312/3/1082.abstract N2 - We tested the hypothesis that differential sensitivity to ethanol of synaptic GABAA somatic and dendritic inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons could be due to differences in the extent of GABAB receptor activity at GABAergic synapses in these two hippocampal subfields. Our present results show that dendritic (distally evoked) GABA IPSCs contain a larger GABAB IPSC component of the total GABA IPSC than the somatic (proximally evoked) subfield. The inhibition of GABAB receptors by pretreatment of hippocampal slices with CGP-52432 [3[[(3,4-dichlorophenyl)methyl]amino]propyl](diethoxymethyl) phosphinic acid], a selective GABAB receptor antagonist, changes the basal ethanol-insensitive, distally evoked GABAA IPSCs to become more sensitive to ethanol. In addition, paired-pulse stimulation of the proximal and distal subfields of hippocampal pyramidal neurons shows that ethanol alone increases the probability of GABA release at proximal but not distal regions. Changes by ethanol on the probability of GABA release are only seen at distal locations during GABAB blockade. Finally, when the modulation of presynaptic GABAB receptors is minimized by the local application of 10 mM GABA directly onto somatic or dendritic GABAergic synaptic regions, postsynaptic GABAB receptors seem to exert significant negative (inhibiting) influence on the effects of ethanol on GABAA IPSCs in the distal subfields of CA1 pyramidal neurons. Together, our data suggest that differences in both presynaptic and postsynaptic GABAB receptor activity at these GABAergic synapses may modulate the differential ethanol sensitivity of proximal and distal GABA IPSCsA in hippocampal CA1 pyramidal neurons. The American Society for Pharmacology and Experimental Therapeutics ER -