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在大鼠的高多巴胺能状态下,蔗糖需求的弹性增加。

Increased elasticity of sucrose demand during hyperdopaminergic states in rats.

机构信息

Department of Population Health Sciences, Unit Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.

出版信息

Psychopharmacology (Berl). 2022 Mar;239(3):773-794. doi: 10.1007/s00213-022-06068-x. Epub 2022 Jan 31.

Abstract

RATIONALE

Deficits in cost-benefit decision-making are a core feature of several psychiatric disorders, including substance addiction, eating disorders and bipolar disorder. Mesocorticolimbic dopamine signalling has been implicated in various processes related to cognition and reward, but its precise role in reward valuation and cost-benefit trade-off decisions remains incompletely understood.

OBJECTIVES

We assessed the role of mesocorticolimbic dopamine signalling in the relationship between price and consumption of sucrose, to better understand its role in cost-benefit decisions.

METHODS

Dopamine neurons in the ventral tegmental area (VTA) were chemogenetically activated in rats, and a behavioural economics approach was used to quantify the relationship between price and consumption of sucrose. Motivation for sucrose was also assessed under a progressive ratio (PR) schedule of reinforcement. To further gauge the role of dopamine in cost-benefit trade-offs for sucrose, the effects of treatment with D-amphetamine and the dopamine receptor antagonist alpha-flupentixol were assessed.

RESULTS

Chemogenetic activation of VTA dopamine neurons increased demand elasticity, while responding for sucrose under a PR schedule of reinforcement was augmented upon stimulation of VTA dopamine neurons. Treatment with amphetamine partially replicated the effects of chemogenetic dopamine neuron activation, whereas treatment with alpha-flupentixol reduced free consumption of sucrose and had mixed effects on demand elasticity.

CONCLUSIONS

Stimulation of mesocorticolimbic dopaminergic neurotransmission altered cost-benefit trade-offs in a complex manner. It reduced the essential value of palatable food, increased incentive motivation and left free consumption unaltered. Together, these findings imply that mesocorticolimbic dopamine signalling differentially influences distinct components of cost expenditure processes aimed at obtaining rewards.

摘要

原理

成本效益决策的缺陷是包括物质成瘾、饮食失调和双相情感障碍在内的几种精神疾病的核心特征。中脑边缘多巴胺信号已被牵涉到与认知和奖励相关的各种过程中,但它在奖励评估和成本效益权衡决策中的精确作用仍不完全清楚。

目的

我们评估了中脑边缘多巴胺信号在价格和蔗糖消费之间的关系中的作用,以更好地了解其在成本效益决策中的作用。

方法

化学遗传学激活大鼠腹侧被盖区(VTA)中的多巴胺神经元,并采用行为经济学方法来量化蔗糖价格和消费之间的关系。在递增比率(PR)强化时间表下也评估了蔗糖的动机。为了进一步衡量多巴胺在蔗糖成本效益权衡中的作用,评估了 D-苯丙胺和多巴胺受体拮抗剂α-氟哌啶醇的治疗效果。

结果

VTA 多巴胺神经元的化学遗传学激活增加了需求弹性,而 VTA 多巴胺神经元的刺激增加了蔗糖的 PR 时间表下的反应。安非他命的治疗部分复制了化学遗传学多巴胺神经元激活的作用,而α-氟哌啶醇的治疗降低了蔗糖的自由消费,并对需求弹性产生了混合影响。

结论

中脑边缘多巴胺能神经传递的刺激以复杂的方式改变了成本效益权衡。它降低了美味食物的基本价值,增加了激励动机,而自由消费则保持不变。这些发现表明,中脑边缘多巴胺信号对获得奖励的成本支出过程的不同组成部分有不同的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f71/8891210/7a53f173f075/213_2022_6068_Fig1_HTML.jpg

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