The N-methyl-d-aspartate (NMDA) receptor-selective antagonist, amino-5-phosphonopentanoate (AP5), decreases action potential (AP) firing rate in acute high-fat diet (HFD), but not control, dorsal motor nucleus of the vagus (DMV) neurons. A: representative traces from a gastric-projecting DMV neuron from a control diet rat, current clamped at a potential that allowed AP firing of ~1 Hz. Perfusion with AP5 (25 μM) had no effect on AP firing rate in 7/10 neurons tested (3 rats). Subsequent application of 6,7-dinitroquinoxaline-2,3-dione (DNQX) (30 μM) decreased AP firing rate in 8/10 neurons tested (3 rats). B: representative traces from a gastric-projecting DMV neuron from an acute HFD rat, current clamped at a potential to allow AP firing of ~1 Hz. Perfusion with AP5 (25 μM) decreased AP firing in all 5 neurons (from 3 rats) tested. Subsequent application of DNQX (30 μM) did not affect AP firing rate further. C: graphical summary of the responses of control (left; n = 10 neurons from 3 rats) and acute HFD (right; n = 5 neurons from 3 rats) gastric-projecting DMV neurons to perfusion with AP5 and DNQX. Note that AP5 decreased the firing rate in all acute HFD neurons but in only a minority of control neurons. *P < 0.05 vs. baseline (Student’s paired t-test), #P < 0.05 vs. control (Student’s paired t-test). D: graphical summary of the proportion of gastric-projecting DMV neurons responding to AP5 with a decrease in AP firing rate.*P < 0.05 vs. control (χ2-test).