Skov Louise J, Jensen Morten, Christiansen Søren H, Ratner Cecilia, Woldbye David P D, Holst Birgitte
Section for Metabolic Receptology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark.
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Int J Mol Sci. 2017 Apr 26;18(5):914. doi: 10.3390/ijms18050914.
Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions. However, during novel environment stress Ghr-R mice showed increased food intake and energy expenditure compared to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the response to stress. Ghr-R mice also showed increased cocaine-induced locomotor activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin signaling for the reward-related effects of activation of VTA neurons. Overall, our data suggest that re-introduction of the Ghr-R in the mesolimbic reward system of Ghr-R knockout mice increases the level of activation induced by both cocaine and novelty stress.
腹侧被盖区（VTA）神经元中的胃饥饿素受体（Ghr-R）信号传导可调节多巴胺能功能以及美味食物和滥用药物与奖赏相关的效应。在本研究中，我们在胃饥饿素受体基因敲除小鼠（Ghr-R KO小鼠）的VTA神经元中重新引入了Ghr-R，以专门研究组成型激活的Ghr-R对VTA神经元信号传导的重要性。我们的结果表明，在基础条件下，在VTA中重新引入Ghr-R对体重或食物摄入量没有影响。然而，在新环境应激期间，与Ghr-R KO小鼠相比，Ghr-R小鼠的食物摄入量和能量消耗增加，这表明Ghr-R信号传导在应激反应中的重要性。与Ghr-R KO小鼠相比，Ghr-R小鼠对可卡因诱导的运动活动也增加，这突出了胃饥饿素信号传导对激活VTA神经元与奖赏相关效应的重要性。总体而言，我们的数据表明，在Ghr-R KO小鼠的中脑边缘奖赏系统中重新引入Ghr-R会增加可卡因和新异应激诱导的激活水平。
