Additive satiety-delaying effects of capsaicin-induced visceral deafferentation and NMDA receptor blockade suggest separate pathways

Both ablation of visceral afferents and blockade of NMDA receptor-mediated glutamatergic transmission by MK-801 result in overconsumption of sucrose s olution and other food, apparently by interrupting Visceral signals and thu s delaying satiation. If these two manipulations act on the same pathway, n amely, the propagation of vagal afferent signals to NTS neurons, their effe cts would be expected to be non-additive. To test this hypothesis, two grou ps of rats - one with prior systemic capsaicin (n = 11) and one with vehicl e treatment (n = 10) - were trained to drink 15% sucrose solution after 15 h food deprivation every 3-4 days, and then injected with MK-801 (100 mug/k g, i.p.) or saline. Both capsaicin and MK-801 produced the expected signifi cant (p<.001) increase in 30 and 60 min sucrose intake if compared to their respective controls. Administration of MK-801 to capsaicin-treated rats fu rther increased 60 min sucrose intake significantly (p<.001) in a fully add itive fashion. These results suggest that the two treatments do not impinge on the same neural pathway to delay satiation. MK-801 may interfere with s ignals from capsaicin-resistant vagal afferents, or alternatively may act o n other areas in the brain or periphery. (C) 2000 Elsevier Science Inc. All rights reserved.