Behavior-associated and post-consumption glucose entry into the nucleus accumbens extracellular space during glucose free-drinking in trained rats
Behavior-associated and post-consumption glucose entry into the nucleus accumbens extracellular space during glucose free-drinking in trained rats
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DOI：
10.3389/fnbeh.2015.00173
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发表时间：
2015-07-02
影响因子：
3
通讯作者：
Kiyatkin, Eugene A.
中科院分区：
文献类型：
--
作者：
Wakabayashi, Ken T.;Kiyatkin, Eugene A.
葡萄糖是脑细胞代谢活动的主要能量底物，它从动脉血中的适当输送对神经活动和正常的大脑功能至关重要。葡萄糖也是一种独特的天然增强剂，支持饮用葡萄糖的行为，而不会缺乏食物或水。虽然已知葡萄糖通过梯度依赖的促进扩散进入脑组织，但尚不清楚葡萄糖水平在自然行为中是如何变化的，以及摄入的葡萄糖的直接中枢作用是否参与调节葡萄糖饮酒行为。在这里，我们使用高速安培法的葡萄糖生物传感器来检测训练有素的大鼠在无限制饮糖过程中伏隔核(NAC)细胞外葡萄糖的时相和紧张性变化模式。我们发现，饮酒行为是高度周期性的，与细胞外葡萄糖水平相对较大和持续的增加有关。这些增加有两个明显的组成部分：一个是高度阶段性的，但相对较小的与行为相关的上升，另一个是由于消耗的葡萄糖进入大脑的细胞外空间而导致的更大的紧张性上升。摄取后NAC血糖的大幅增加在停止饮酒几分钟后开始，并与不饮酒时间一致，这表明摄取的葡萄糖的中枢作用可能通过在重复饮酒之间导致活动暂停来抑制饮酒行为。最后，通过胃内导管主动的、行为介导的和被动的葡萄糖输送之间的NAC葡萄糖反应的差异证实了积极的行为也与脑细胞对代谢葡萄糖的利用有关。
Glucose is the primary energetic substrate for the metabolic activity of brain cells and its proper delivery from the arterial blood is essential for neural activity and normal brain functions. Glucose is also a unique natural reinforcer, supporting glucose-drinking behavior without food or water deprivation. While it is known that glucose enters brain tissue via gradient dependent facilitated diffusion, it remains unclear how glucose levels are changed during natural behavior and whether the direct central action of ingested glucose can be involved in regulating glucose-drinking behavior. Here, we used glucose biosensors with high-speed amperometry to examine the pattern of phasic and tonic changes in extracellular glucose in the nucleus accumbens (NAc) during unrestricted glucose-drinking in well-trained rats. We found that the drinking behavior is highly cyclic and is associated with relatively large and prolonged increases in extracellular glucose levels. These increases had two distinct components: a highly phasic but relatively small behavior related rise and a larger tonic elevation that results from the arrival of consumed glucose into the brain's extracellular space. The large post-ingestion increases in NAc glucose began minutes after the cessation of drinking and were consistently associated with periods of non-drinking, suggesting that the central action of ingested glucose could inhibit drinking behavior by inducing a pause in activity between repeated drinking bouts. Finally, the difference in NAc glucose responses found between active, behavior-mediated and passive glucose delivery via an intra-gastric catheter confirms that motivated behavior is also associated with metabolic glucose use by brain cells.