Figure 5

5-(6-Amino-2-(phenethylthio)-9H-purin-9-yl)- N -ethyl-3,4-dihydroxytetrahydrofuran-2-carboxamide (VT7) increases hippocampal N -methyl- d -aspartate receptor component of field excitatory postsynaptic potentials (NMDA-fEPSPs) and its action depends on d -serine. Averaged timecourse of changes in NMDA-fEPSPs recorded in hippocampal slices. Points: mean ± SEM. Horizontal bar, VT7 application (50 nM). Inset on top: representative NMDA-fEPSP traces recorded in control conditions, in the presence of VT7 and during washout, as indicated (same time points as Figure 1). Vertical scale bar: 0.1 mV, horizontal scale bar: 20 ms. Slices treated with adenosine deaminase (ADA), 1 U/ml. (A) Application of VT7 enhances NMDA-fEPSP slopes (n = 9/2). (B) Blocking of the NMDAR d-serine site completely prevents the VT7 effect on NMDA-fEPSP slopes. Slices pretreated with 5,7-dicholorokynurenic acid (DCKA) (750 nM) for 20 minutes (last 10 minutes in the graph) before VT7 application and then continuously treated (n = 11/3). (C) Degradation of d-serine block VT7-mediated NMDA modulation. Slices pretreated for 1 h and then continuously superperfused with d-amino acid oxidase (DAAO) (0.1 U/ml) and catalase (300 U/ml). Cotreatment with VT7 did not increase NMDA-fEPSPs slope (n = 7/3).