BACKGROUND:Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake. METHODS:Here, we used designer receptors exclusively activated by designer drugs (DREADD) technology to determine the effects of enhancing DA neuronal activity on feeding behaviour. We chemogenetically activated selective midbrain DA neuronal subpopulations and assessed the effects on feeding microstructure in rats. RESULTS:Treatment with the psychostimulant drug amphetamine or the selective DA reuptake inhibitor GBR 12909 significantly suppressed food intake. Selective chemogenetic activation of DA neurons in the ventral tegmental area (VTA) was found to reduce meal size, but had less impact on total food intake. Targeting distinct VTA neuronal pathways revealed that specific activation of the mesolimbic pathway towards nucleus accumbens (NAc) resulted in smaller and shorter meals. In addition, the meal frequency was increased, rendering total food intake unaffected. The disrupted feeding patterns following activation of VTA DA neurons or VTA to NAc projection neurons were accompanied by locomotor hyperactivity. Activation of VTA neurons projecting towards prefrontal cortex or amygdala, or of DA neurons in the substantia nigra, did not affect feeding behaviour. CONCLUSIONS:Chemogenetic activation of VTA DA neurons or VTA to NAc pathway disrupts feeding patterns. Increased activity of mesolimbic DA neurons appears to both promote and reduce food intake, by facilitating both the initiation and cessation of feeding behaviour.

译文

背景:大脑中的多巴胺(DA)信号对于喂养行为是必需的,并且DA系统的变化与肥胖有关。但是,DA在控制食物摄入中的确切作用仍存在争议。一方面,食物奖励和动机与增强的DA活动有关。另一方面,增加DA信号传导的抗精神兴奋药会抑制食物摄入。这就提出了一个问题,即内源性DA神经元活性如何调节进食,增强DA神经元活性是否会促进或减少食物摄入。
方法:在这里,我们使用了仅由设计药物(DREADD)技术激活的设计受体来确定增强DA神经元活性对喂养行为的影响。我们用化学方法激活了选择性中脑DA神经元亚群,并评估了对大鼠进食微结构的影响。
结果:用精神刺激药苯丙胺或选择性DA再摄取抑制剂GBR 12909治疗可显着抑制食物摄入。发现腹侧被盖区(VTA)中DA神经元的选择性化学生成激活可减少进餐量,但对总食物摄入量的影响较小。靶向不同的VTA神经元途径揭示了向伏隔核(NAc)的中脑边缘途径的特异性激活导致进食量减少和进食减少。此外,进餐频率增加,使总食物摄入量不受影响。 VTA DA神经元或VTA变为NAc投影神经元激活后,进食方式受到破坏,并伴有运动亢进。朝向前额叶皮层或杏仁核的VTA神经元或黑质中的DA神经元的激活不影响喂养行为。
结论:VTA DA神经元或VTA向NAc途径的化学活化会破坏喂养方式。中脑边缘DA神经元的活动增加似乎通过促进进食行为的开始和停止而促进和减少了食物的摄入。

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