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Wistar大鼠在不进行禁水、糖精/蔗糖消退或延长获取训练的情况下,能够习得并维持20%乙醇的自我给药行为。

Wistar rats acquire and maintain self-administration of 20 % ethanol without water deprivation, saccharin/sucrose fading, or extended access training.

作者信息

Augier E, Flanigan M, Dulman R S, Pincus A, Schank J R, Rice K C, Kejun C, Heilig M, Tapocik J D

机构信息

Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA,

出版信息

Psychopharmacology (Berl). 2014 Dec;231(23):4561-8. doi: 10.1007/s00213-014-3605-3. Epub 2014 May 25.

DOI:10.1007/s00213-014-3605-3
PMID:24858375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4988093/
Abstract

RATIONALE

Operant self-administration (SA) is an important model of motivation to consume ethanol (EtOH), but low rates of voluntary consumption in rats are thought to necessitate water deprivation and saccharin/sucrose fading for acquisition of responding.

OBJECTIVES

Here, we sought to devise an effective model of SA that does not use water deprivation or saccharin/sucrose fading.

METHODS

First, we tested if Wistar rats would acquire and maintain SA behavior of 20 % EtOH under two conditions, water deprivation (WD) and non-water deprivation (NWD). Second, we tested the efficacy of our SA procedure by confirming a prior study which found that the NK1 antagonist L822429 specifically blocked stress-induced reinstatement of EtOH seeking but not SA. Finally, we assessed the effect of naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress EtOH SA in rodents.

RESULTS

Lever presses (LPs) and rewards were consistent with previous reports that utilized WD and saccharin/sucrose fading. Similar to previous findings, we found that L822429 blocked stress-induced reinstatement but not baseline SA of 20 % EtOH. Moreover, naltrexone dose-dependently decreased alcohol intake and motivation to consume alcohol for rats that are self-administering 20 % EtOH.

CONCLUSIONS

Our findings provide a method for voluntary oral EtOH SA in rats that is convenient for experimenters and eliminates the potential confound of sweeteners in EtOH-operant SA studies. Unlike models that use intermittent access to 20 % EtOH, this method does not induce escalation, and based on pharmacological experiments, it appears to be driven by the positive reinforcing effects of EtOH.

摘要

原理

操作性自我给药(SA)是乙醇(EtOH)消费动机的重要模型,但大鼠自愿消费率较低,据认为需要进行水剥夺以及糖精/蔗糖淡化处理才能获得反应。

目的

在此,我们试图设计一种不使用水剥夺或糖精/蔗糖淡化的有效SA模型。

方法

首先,我们测试了Wistar大鼠在水剥夺(WD)和非水剥夺(NWD)两种条件下是否会习得并维持20%乙醇的SA行为。其次,我们通过证实一项先前的研究来测试我们的SA程序的有效性,该研究发现NK1拮抗剂L822429能特异性阻断应激诱导的乙醇觅求行为的恢复,但不能阻断SA。最后,我们评估了纳曲酮的作用,纳曲酮是一种经美国食品药品监督管理局(FDA)批准用于治疗酒精依赖的药物,已被证明能抑制啮齿动物的乙醇SA。

结果

杠杆按压(LPs)和奖励与先前利用WD和糖精/蔗糖淡化的报告一致。与先前的发现相似,我们发现L822429能阻断应激诱导的恢复,但不能阻断20%乙醇的基线SA。此外,纳曲酮能剂量依赖性地减少自行服用20%乙醇的大鼠的酒精摄入量和饮酒动机。

结论

我们的研究结果为大鼠自愿口服乙醇SA提供了一种方法,这对实验者来说很方便,并且消除了乙醇操作性SA研究中甜味剂的潜在混杂因素。与使用间歇性获取20%乙醇的模型不同,这种方法不会导致摄入量增加,并且根据药理学实验,它似乎是由乙醇的正性强化作用驱动的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/3162daeecacd/nihms806651f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/c8d855876982/nihms806651f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/19cab52a3464/nihms806651f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/3162daeecacd/nihms806651f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/c8d855876982/nihms806651f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/19cab52a3464/nihms806651f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec5/4988093/3162daeecacd/nihms806651f3.jpg

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