Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA.
Nat Neurosci. 2011 Nov 13;14(12):1562-8. doi: 10.1038/nn.2977.
We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.
我们开发了一种用于量化营养物质奖赏价值的检测方法,并利用该方法分析了代谢状态和瘦素的影响。在该检测方法中,小鼠可以在两个吸管之间进行选择,一个吸管提供水,与光遗传学激活多巴胺能(DA)神经元偶联,另一个吸管提供天然或人工甜味剂。该检测方法测量了甜味剂相对于诱导 DA 神经元光遗传学激活的舔舐的奖赏价值。与蔗糖相比,小鼠更喜欢光遗传学刺激 DA 神经元,但不喜欢三氯蔗糖。然而,小鼠更喜欢三氯蔗糖加光遗传学刺激而不是蔗糖。我们发现,食物限制增加了蔗糖相对于三氯蔗糖加光遗传学刺激的价值,而瘦素则降低了它。我们的数据表明,瘦素抑制了蔗糖驱动味觉独立的 DA 神经元激活的能力,并为瘦素对食物摄入的影响机制提供了新的见解。