Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback.
Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback.
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DOI：
10.1152/ajpregu.00097.2016
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发表时间：
2016-09
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通讯作者：
S. J. Terrill;Kellie M. Hyde;Kristen E Kay;H. Greene;Calyn B Maske;Amanda E Knierim;Jon F. Davis;Diana L. Williams
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作者：
S. J. Terrill;Kellie M. Hyde;Kristen E Kay;H. Greene;Calyn B Maske;Amanda E Knierim;Jon F. Davis;Diana L. Williams
下丘脑的食欲素神经元投射到许多大脑区域，包括与动机和觅食行为有关的腹侧被盖区(VTA)。在这里，我们讨论了在VTA中外源性给予食欲素-A和内源性食欲素1受体(OX1R)激活如何影响摄食行为。我们假设，食欲素-A和氧合酶1R拮抗剂SB334867被注射到VTA，剂量低于脑室注射时的效应阈值，将在多种测试情况下影响美味食物的摄入量。我们首先使用了一种享乐喂养模型，在该模型中，饱足的大鼠选择性地食用高脂肪饮食(HFD)。在这个模型中，VTA内注射食欲素-A刺激了额外的食物消费和增加了HFD的摄入量。在随机喂养的大鼠中，每天进行30分钟的测试，VTA内注射增食欲素-A也增加了HFD和0.1M蔗糖的摄入量。对舔食模式的进一步分析表明，VTA食欲素-A增加了一顿饭的大小，并且只在一餐接近结束时才增加了舔食爆发的大小。与这一发现一致的是，阈值以下剂量的VTA增食素-A可以防止胃肠道营养输注引起的摄取抑制。令人惊讶的是，VTA内注射增食欲素-A对蔗糖颗粒的操作反应没有影响，这是一个渐进的强化比率计划。我们发现，双侧VTA注射选择性OX1R拮抗剂SB334867抑制0.1M的蔗糖摄入量，这支持了内源性VTA OX1R刺激的作用。综上所述，我们的数据表明，VTA中的OX1R活动促进了食物的摄入，可能是通过抵消进食后的负反馈，这些负反馈通常会抑制进食。
Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal.