Substance P suppresses evoked IPSCs primarily via activation of NK1 receptors. A, Time course of evoked IPSC amplitudes (eIPSC Ampl) during superfusion of substance P (SubP, 300 nm) and picrotoxin (Pictx, 100 μm) in an unidentified neuron. Each point is the mean of two consecutive evoked IPSCs. B, Averaged traces of evoked IPSCs before (Pre) and during substance P and picrotoxin. C, Averaged traces in response to paired stimuli (IPSC1–2 interval, 70 ms) with IPSC1 normalized (left) before and during substance P. D, Bar chart of the mean amplitude and paired-pulse ratio (PP ratio) of evoked IPSCs recorded from unidentified PAG neurons in the presence of substance P, expressed as a percentage of the predrug control (Ctl) level, in neurons preincubated in the NK1 receptor antagonist L732,138 (20 μm, NK1) and a combination of the NK1, NK2, and NK3 receptor antagonists L732,138 (20 μm), GR159897 (3 μm), and SB218795 (3 μm) (NK1–3) compared with neurons that did not undergo preincubation. **p < 0.01; ##p < 0.0001. A–C are taken from one neuron.