Inconsistencies in the hypophagic action of intracerebroventricular insulin in mice.
Inconsistencies in the hypophagic action of intracerebroventricular insulin in mice.
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DOI：
10.1016/j.physbeh.2015.08.038
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发表时间：
2015-11-01
影响因子：
2.9
通讯作者：
Langhans W
中科院分区：
文献类型：
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作者：
Mc Allister E;Pacheco-Lopez G;Woods SC;Langhans W
胰岛素抑制进食后，其脑室内（ICV）给药在多种物种和各种条件下。然而，报告的结果并不一致，即ICV胰岛素并不总是减少食物摄入。造成这种差异的原因在很大程度上是未知的。我们以小鼠为模型，对注入第三脑室（i3vt）的胰岛素和载药进行了几项交叉试验，以验证最近的i3vt手术经验有助于ICV胰岛素对食物摄入影响的变异性。使用注射间隔两天的交叉设计，我们发现胰岛素（0.4 μ U/只）相对于对照剂，在第一次试验中接受对照剂和第二次试验中接受胰岛素的小鼠显著减少了食物摄入量，而在第一次试验中接受胰岛素和第二次试验中接受对照剂的小鼠没有这种影响。更高剂量（i3vt 4.0和40.0µU/小鼠）对食物摄入量没有影响。当注射间隔7天时，胰岛素减少了食物摄入量，没有交叉效应。小鼠在接受高剂量i3vt胰岛素后没有减少食物摄入量，但在接受i3vt输注黑素皮质素受体激动剂melanotin - ii （MT-II）后却减少了食物摄入量，这表明调节胰岛素对饮食影响的下丘脑黑素皮质素系统的功能没有受到胰岛素影响的任何干扰，而且这种干扰发生在黑素皮质素受体的上游。总的来说，我们的研究结果表明，基于先前实验情况经验的联想效应可能会损害胰岛素引起的进食抑制。
Insulin inhibits eating after its intracerebroventricular (ICV) administration in multiple species and under a variety of conditions. Nevertheless, the results across reports are inconsistent in that ICV insulin does not always reduce food intake. The reasons for this variability are largely unknown. Using mice as a model, we performed several crossover trials with insulin vs. vehicle when infused into the third cerebral ventricle (i3vt) to test the hypothesis that recent experience with the i3vt procedure contributes to the variability in the effect of ICV insulin on food intake. Using a cross-over design with two days between injections, we found that insulin (0.4 µU/mouse) significantly reduced food intake relative to vehicle in mice that received vehicle on the first and insulin on the second trial, whereas this effect was absent in mice that received insulin on the first and vehicle on the second trial. Higher doses (i3vt 4.0 and 40.0 µU/mouse) had no effect on food intake in this paradigm. When injections were spaced 7 days apart, insulin reduced food intake with no crossover effect. Mice that did not reduce food intake in response to higher doses of i3vt insulin did so in response to i3vt infusion of the melanocortin receptor agonist melanotan-II (MT-II), indicating that the function of the hypothalamic melanocortin system, which mediates the effect of insulin on eating, was not impaired by whatever interfered with the insulin effect, and that this interference occurred upstream of the melanocortin receptors. Overall, our findings suggest that associative effects based on previous experience with the experimental situation can compromise the eating inhibition elicited by i3vt administered insulin.