Compulsive eating behavior is hypothesized to be driven in part by reward deficits likely due to neuroadaptations to the mesolimbic dopamine (DA) system. Therefore, the aim of this study was to assess deficits in reward system functioning and mesolimbic DA after alternating a standard chow with palatable diet, a model of compulsive eating. In this model, rats in the control group (Chow/Chow) are provided a standard chow diet 7 days a week, while the experimental group (Chow/Palatable) is provided chow for 5 days a week ("C Phase"), followed by 2 days of access to a highly palatable sucrose diet ("P Phase"). We first tested the sensitivity to d-Amphetamine's stimulatory, reward-enhancing, and primary rewarding effects using a locomotor activity assay, an intracranial self-stimulation (ICSS) procedure, and a conditioned place preference test, respectively. We then quantified DA release in the nucleus accumbens (NAc) shell after treatment with d-Amphetamine using in vivo microdialysis, quantified levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA using quantitative polymerase chain reaction (qPCR), and lastly, quantified baseline extracellular DA and function of DAT in vivo using quantitative "no-net-flux" microdialysis. Chow/Palatable rats displayed blunted d-Amphetamine-induced locomotor activity, insensitivity to d-Amphetamine potentiation of ICSS threshold, and decreased place preference for d-Amphetamine during the P Phase. We found that Chow/Palatable rats had blunted DA efflux following d-Amphetamine treatment. Furthermore, DAT mRNA was increased in Chow/Palatable rats during the P Phase. Finally, quantitative "no-net-flux" microdialysis revealed reduced extracellular baseline DA and DAT function in Chow/Palatable rats. Altogether, these results provide evidence of reduced reward system functioning and related neuroadaptations in the DA and DAT systems in this model of compulsive eating. Reward deficits, resulting from repeated overeating, may in turn contribute to the perpetuation of compulsive eating behavior.

中文翻译：

---

在强迫性进食行为的大鼠模型中，奖励敏感性不足。

据推测，强迫性进食行为部分是由于可能由于中脑边缘多巴胺（DA）系统的神经适应而导致的奖赏不足所致。因此，本研究的目的是评估将标准食物与可口饮食（一种强迫性饮食的模型）交替使用后，奖励系统功能和中脑边缘DA的缺陷。在此模型中，对照组（Chow / Chow）的大鼠每周7天提供标准的日常饮食，而实验组（Chow / Palatable）则每周5天提供“ Chow”的食物（“ C期”），然后接受高度美味的蔗糖饮食2天（“ P阶段”）。我们首先使用运动活动分析，颅内自我刺激（ICSS）程序测试了对d-苯丙胺的刺激，增强奖励和主要奖励作用的敏感性，和有条件的地方偏好测试。然后，我们使用体内微量透析法对d-苯丙胺处理后的伏隔核（NAc）壳中的DA释放进行了定量，使用定量聚合酶链反应（qPCR）对酪氨酸羟化酶（TH）和多巴胺转运蛋白（DAT）mRNA的定量进行了定量，最后，使用定量的“无净通量”微透析对体内的基线细胞外DA和DAT进行定量。松鼠/可食大鼠在P期表现出钝性的d-苯丙胺诱导的运动活性，对ICSS阈值对d-苯丙胺增强的不敏感性以及对d-苯丙胺的位置偏好降低。我们发现在d-苯丙胺治疗后，Chow / Palatable大鼠的DA外排变钝。此外，在P期中，Chow /可口大鼠中的DAT mRNA增加。最后，定量的“无净通量”微透析显示，Chow /可口大鼠的细胞外基线DA和DAT功能降低。总之，这些结果提供了这种强迫性进食模型中DA和DAT系统中奖励系统功能降低和相关神经适应降低的证据。反复暴饮暴食导致的奖励不足，反过来又可能导致强迫性进食行为长期存在。