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多巴胺受体D4拮抗剂与CB2受体激动剂共同给药可减少小鼠对美味食物的暴饮暴食。

Coadministration antagonist dopamine receptor D4 with CB2 receptor agonist decreases binge-like intake of palatable food in mice.

作者信息

Rodríguez-Serrano Luis Miguel, López-Castillo Ana Paola, Cabrera-Mejía María Cristina, Cedillo-Figueroa Ana Sofía, Zepeda-Ortigosa Nyahn, Carregha-Lozano Carolina, Chávez-Hernández María Elena

机构信息

Facultad de Psicología, Universidad Anáhuac México, Huixquilucan, Estado de México, Mexico.

出版信息

Front Behav Neurosci. 2025 Apr 29;19:1572374. doi: 10.3389/fnbeh.2025.1572374. eCollection 2025.

Abstract

INTRODUCTION

Food intake is regulated by two systems: homeostatic and hedonic. An imbalance between these systems can induce overconsumption, such as binge eating disorder (BED), and is associated with dysregulation of the dopamine reward system. The cannabinoid type 2 receptor (CB2R) has been identified in dopamine neurons and may play an important role in motivated behaviors, including food intake. Nevertheless, the interaction between the dopamine D4 (DRD4) receptor and CB2R in binge-like intake has not yet been identified. Therefore, the present study aims to evaluate the effects of intraperitoneal administration of DRD4 antagonist (L-745870), as well as the coadministration of DRD4 antagonist with either CB2R agonist (HU308) or antagonist (AM630), on binge-like intake of palatable food (PF) in adult male mice.

METHODS

We used adult male 34 C57BL6/J mice. All animals were housed individually and had access to standard diet (SD) and water. To evaluate binge-like intake, the animals had 1 h of access to PF during 12 baseline binge eating test (BET) sessions. Mice were then randomly assigned to the following treatment groups: 1) vehicle; 2) L-745870; 3) L-745870-HU308, 4) L-745870+AM630 to be evaluated under the effect of treatments for three additionally BET sessions.

RESULTS

Our results show that DRD4 antagonist reduced binge-like intake of PF, and that a coadministration with a CB2R agonist induced an even more pronounced reduction of binge-like intake.

CONCLUSION

These findings suggest an interaction between the dopaminergic and endocannabinoid systems in the modulation of binge-like intake of PF in adult mice, where CB2R activation participates in modulating reward pathways and reducing binge-like behavior.

摘要

引言

食物摄入由两种系统调节:稳态系统和享乐系统。这两种系统之间的失衡会导致过度消费,如暴饮暴食症(BED),并与多巴胺奖赏系统的失调有关。已在多巴胺神经元中发现了大麻素2型受体(CB2R),它可能在包括食物摄入在内的动机行为中发挥重要作用。然而,多巴胺D4(DRD4)受体与CB2R在类似暴饮暴食行为中的相互作用尚未明确。因此,本研究旨在评估腹腔注射DRD4拮抗剂(L-745870),以及DRD4拮抗剂与CB2R激动剂(HU308)或拮抗剂(AM630)联合给药,对成年雄性小鼠美味食物(PF)类似暴饮暴食行为的影响。

方法

我们使用了34只成年雄性C57BL6/J小鼠。所有动物单独饲养,可获取标准饮食(SD)和水。为评估类似暴饮暴食行为,在12次基线暴饮暴食测试(BET)期间,让动物有1小时获取PF的时间。然后将小鼠随机分为以下治疗组:1)赋形剂组;2)L-745870组;3)L-745870-HU组合;4)L-745870+AM630组,在另外3次BET期间评估治疗效果。

结果

我们的结果表明,DRD4拮抗剂减少了PF的类似暴饮暴食行为,并且与CB2R激动剂联合给药导致类似暴饮暴食行为的减少更为显著。

结论

这些发现表明,多巴胺能系统和内源性大麻素系统在调节成年小鼠PF类似暴饮暴食行为中存在相互作用,其中CB2R激活参与调节奖赏途径并减少类似暴饮暴食行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fb/12069467/1847b4654067/fnbeh-19-1572374-g001.jpg

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