Neuroscience Program, University of Wyoming, Laramie, WY, USA.
Neuroscience Program, University of Michigan, Ann Arbor, MI, USA.
Neuropsychopharmacology. 2017 Nov;42(12):2354-2364. doi: 10.1038/npp.2017.57. Epub 2017 Mar 15.
Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.
进食的欲望可以被与先前食物体验相关的环境刺激所驱动。识别大脑奖励回路中的适应机制，促进线索诱导的食物寻求，对于理解和预防过度进食和随后的体重增加至关重要。我们利用电生理学、生物化学和 DiI 标记技术，研究了与食物渴望的时间依赖性增加（“渴望的孵化”）相关的伏隔核（NAc）和前额叶皮层（PFC）的功能和结构变化。大鼠自我给予 60%高脂肪或 chow 45mg 丸剂，然后在训练后 1 或 30 天进行渴望孵化测试。选择高脂肪进行比较，以确定美味性是否会对孵化和/或可塑性产生不同的影响。大鼠对两种食物奖励都表现出强烈的渴望孵化，但与高脂肪相关的线索的反应在 1 天和 30 天都大于 chow。此外，以前高脂肪消费的经验降低了 PFC 在两个时间点的树突棘密度。相比之下，在 30 天的时间里，孵化与 NAc 棘密度的增加和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）介导的传递增加有关，在两组中均如此。最后，对 chow 和高脂肪的渴望孵化伴随着钙渗透性和非钙渗透性 AMPAR 的增加。我们的研究结果表明，食物渴望的孵化改变了大脑奖励回路，而宏量营养素组成专门以一种可能促进适应不良的食物寻求行为的方式改变了皮质变化。
