Figure 9.
Nitric oxide synthase (NOS) inhibitors overcome the effects of low ketamine on LTP and somatic EPSPs. A. Co-administration of 100 µM L-NMMA, a broad-spectrum and competitive NOS inhibitor, with 1 µM ketamine for 30 min followed by 2–4 hour drug washout overcame the inhibitory effects of ketamine on LTP (white circles). A single 100 Hz × 1 s HFS was administered at the arrow. The effects of L-NMMA were reversed by 1 mM L-arginine, the natural substrate for NOS (black circles). B. Pre-incubation of slices in 1 µM ketamine plus 5 µM 3-bromo-7-nitroindazole, a potent neuronal NOS inhibitor, ketamine on LTP. C. 3-Bromo-7-nitroindazole (5 µM) also blocked the acute effects of ketamine of somatic EPSPs (gray squares), and had no effect on dendritic EPSPs (white squares). Traces depict representative EPSPs with baseline traces shown as thin lines. Calibration: 1 mV, 5 msec.