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阿立新酸/食欲素受体 1 拮抗剂减弱大鼠对糖精的寻求。

Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist.

机构信息

Department of Neurosciences, Medical University of South Carolina, Basic Science Building 406, 173 Ashley Avenue, MSC 510, Charleston, SC 29425, USA.

出版信息

Psychopharmacology (Berl). 2013 Aug;228(3):499-507. doi: 10.1007/s00213-013-3051-7. Epub 2013 Mar 15.

DOI:10.1007/s00213-013-3051-7
PMID:23494235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3707982/
Abstract

RATIONALE

The orexin (Orx)/hypocretin system has been implicated in reward-seeking, especially for highly salient food and drug rewards. We recently demonstrated that signaling at the OxR1 receptor is involved in sucrose reinforcement and reinstatement of sucrose-seeking elicited by sucrose-paired cues in food-restricted rats. Because sucrose reinforcement has both a hedonic and caloric component, it remains unknown what aspect of this reward drives its reinforcing value.

OBJECTIVES

The present study examined the involvement of the Orx system in operant responding for saccharin, a noncaloric, hedonic (sweet) reward, and in cue-induced reinstatement of extinguished saccharin-seeking in ad libitum-fed vs food-restricted male subjects.

METHODS

Male Sprague Dawley rats were fed ad libitum or food-restricted and trained to self-administer saccharin. We determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) saccharin self-administration and on cue-induced reinstatement of extinguished saccharin-seeking.

RESULTS

SB decreased responding and number of reinforcers earned during FR responding for saccharin and decreased cue-induced reinstatement of extinguished saccharin-seeking. All of these effects were obtained similarly in food-restricted and ad libitum-fed rats.

CONCLUSIONS

These results indicate that signaling at the OxR1 receptor is involved in saccharin reinforcement and reinstatement of saccharin-seeking elicited by saccharin-paired cues regardless of food restriction. These findings lead us to conclude that the Orx system contributes to the motivational effects of hedonic food rewards, independently of caloric value and homeostatic needs.

摘要

原理

食欲素(Orx)/下丘脑分泌素系统与寻求奖励有关,尤其是对高度显著的食物和药物奖励。我们最近证明,OxR1 受体的信号传导参与了蔗糖强化以及在食物限制的大鼠中,由蔗糖配对线索引发的蔗糖寻求的复燃。因为蔗糖强化既有享乐的成分,也有热量的成分,所以尚不清楚是什么方面的奖励驱动了它的强化价值。

目的

本研究检查了食欲素系统在操作反应中的作用,该反应是针对蔗糖的,蔗糖是一种无热量的、享乐的(甜)奖励,以及在自由进食的雄性被试中,由线索引发的蔗糖寻求的消退复燃。

方法

雄性 Sprague Dawley 大鼠自由进食或食物限制,并接受蔗糖自我给药训练。我们确定了 OxR1 受体拮抗剂 SB-334867(SB;10-30mg/kg)预处理对固定比率(FR)蔗糖自我给药和消退的蔗糖寻求的线索诱导复燃的影响。

结果

SB 减少了 FR 蔗糖自我给药过程中的反应和获得的强化物数量,并减少了消退的蔗糖寻求的线索诱导复燃。在食物限制和自由进食的大鼠中,均获得了类似的效果。

结论

这些结果表明,OxR1 受体的信号传导参与了蔗糖强化以及由蔗糖配对线索引发的蔗糖寻求的复燃,而与食物限制无关。这些发现使我们得出结论,食欲素系统有助于享乐性食物奖励的动机效应,而与热量值和体内平衡需求无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/dd4be371e4a3/nihms456215f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/81a4d5b53747/nihms456215f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/9d98d75d4dbb/nihms456215f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/dd4be371e4a3/nihms456215f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/81a4d5b53747/nihms456215f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/9d98d75d4dbb/nihms456215f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af29/3707982/dd4be371e4a3/nihms456215f3.jpg

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