Berthoud H, Patterson L M, Morales S, Zheng H
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
Pharmacol Biochem Behav. 2000 Oct;67(2):371-5. doi: 10.1016/s0091-3057(00)00378-6.
Both ablation of visceral afferents and blockade of NMDA receptor-mediated glutamatergic transmission by MK-801 result in overconsumption of sucrose solution and other food, apparently by interrupting visceral signals and thus delaying satiation. If these two manipulations act on the same pathway, namely, the propagation of vagal afferent signals to NTS neurons, their effects would be expected to be non-additive. To test this hypothesis, two groups of rats - one with prior systemic capsaicin (n=11) and one with vehicle 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 microg/kg, i.p.) or saline. Both capsaicin and MK-801 produced the expected significant (P<.001) increase in 30 and 60 min sucrose intake if compared to their respective controls. Administration of MK-801 to capsaicin-treated rats further increased 60 min sucrose intake significantly (P<.001) in a fully additive fashion. These results suggest that the two treatments do not impinge on the same neural pathway to delay satiation. MK-801 may interfere with signals from capsaicin-resistant vagal afferents, or alternatively may act on other areas in the brain or periphery.
内脏传入神经的消融以及用MK-801阻断NMDA受体介导的谷氨酸能传递，显然都会通过中断内脏信号从而延迟饱腹感，导致蔗糖溶液和其他食物的过度消耗。如果这两种操作作用于同一条通路，即迷走神经传入信号向孤束核（NTS）神经元的传导，那么预期它们的作用将不会叠加。为了验证这一假设，两组大鼠——一组预先进行全身辣椒素处理（n = 11），另一组进行赋形剂处理（n = 10）——每3 - 4天在禁食15小时后训练它们饮用15%的蔗糖溶液，然后注射MK-801（100微克/千克，腹腔注射）或生理盐水。与各自的对照组相比，辣椒素和MK-801均使30分钟和60分钟时的蔗糖摄入量出现预期的显著增加（P <.001）。给经辣椒素处理的大鼠注射MK-801，以完全叠加的方式进一步显著增加了60分钟时的蔗糖摄入量（P <.001）。这些结果表明，这两种处理不会作用于同一条神经通路来延迟饱腹感。MK-801可能会干扰来自对辣椒素不敏感的迷走神经传入信号，或者可能作用于大脑或外周的其他区域。
