Food Restriction Increases Glutamate Receptor-Mediated Burst Firing of Dopamine Neurons
Food Restriction Increases Glutamate Receptor-Mediated Burst Firing of Dopamine Neurons
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DOI：
10.1523/jneurosci.5099-12.2013
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发表时间：
2013-08-21
影响因子：
5.3
通讯作者：
Beckstead, Michael J.
中科院分区：
文献类型：
--
作者：
Branch, Sarah Y.;Goertz, R. Brandon;Beckstead, Michael J.
限制食物摄入增加了药物滥用行为的获得，并增强了这些药物的强化功效。然而，负责喂养状态和药物使用之间的相互作用的神经生理机制在很大程度上是未知的。在这里，我们表明慢性轻度食物限制会增加黑质多巴胺神经元的爆发性放电。来自食物限制小鼠的多巴胺神经元在体内表现出增加的爆发放电，这种效应通过注射精神兴奋剂可卡因（10 mg/kg，i. p.）而增强。食物限制也增强了天冬氨酸诱导的多巴胺神经元在离体脑切片制备的突发发射，与发生在体树突隔室和独立的电路机制的适应一致。增强的爆发式放电持续后10天的自由喂养后，慢性食物限制，但没有观察到一个单一的过夜快速。全细胞膜片钳记录表明，食物限制也增加了电诱发的AMPAR/NMDAR比值，并增加了多巴胺神经元中D2自身受体介导的脱敏。这些结果表明，黑质多巴胺神经元作为一个汇聚点之间的相互作用喂养状态和药物滥用。此外，谷氨酸传输增加与自身受体抑制减少相结合，可以协同工作，以提高药物的疗效，对食物限制。
Restriction of food intake increases the acquisition of drug abuse behavior and enhances the reinforcing efficacy of those drugs. However, the neurophysiological mechanisms responsible for the interactions between feeding state and drug use are largely unknown. Here we show that chronic mild food restriction increases the burst firing of dopamine neurons in the substantia nigra. Dopamine neurons from food-restricted mice exhibited increased burst firing in vivo, an effect that was enhanced by an injection of the psychomotor stimulant cocaine (10 mg/kg, i.p.). Food restriction also enhanced aspartic acid-induced burst firing of dopamine neurons in an ex vivo brain slice preparation, consistent with an adaptation occurring in the somatodendritic compartment and independent of a circuit mechanism. Enhanced burst firing persisted after 10 d of free feeding following chronic food restriction but was not observed following a single overnight fast. Whole-cell patch-clamp recordings indicated that food restriction also increased electrically evoked AMPAR/NMDAR ratios and increased D2 autoreceptor-mediated desensitization in dopamine neurons. These results identify dopamine neurons in the substantia nigra as a convergence point for the interactions between feeding state and drugs of abuse. Furthermore, increased glutamate transmission combined with decreased autoreceptor inhibition could work in concert to enhance drug efficacy in response to food restriction.