Qualitative differences between C57BL/6J and DBA/2J mice in morphine potentiation of brain stimulation reward and intravenous self-administration.
Qualitative differences between C57BL/6J and DBA/2J mice in morphine potentiation of brain stimulation reward and intravenous self-administration.
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DOI：
10.1007/s00213-009-1732-z
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发表时间：
2010-02
影响因子：
3.4
通讯作者：
Wise, Roy A.
中科院分区：
文献类型：
--
作者：
Elmer, Greg I.;Pieper, Jeanne O.;Hamilton, Lindsey R.;Wise, Roy A.
关键词：
C57 BL/6 J和DBA/2 J小鼠是用于鉴定阿片类药物成瘾中感兴趣的染色体区域和神经化学机制的最常见的基因型。不幸的是，在口服两瓶选择程序之外，有限的，有时是有争议的证据可用于确定他们对吗啡奖励作用的相对敏感性。本研究的目的是利用经典的药物滥用倾向的模型，以确定相对敏感性的奖励效应的吗啡。在两种基因型中研究了吗啡或安非他明增强外侧下丘脑脑刺激和静脉内吗啡自我给药（在固定比例方案中的三个剂量和渐进比例方案中的最高剂量）的能力。在两种测量中，C57和DBA小鼠对吗啡的反应显著不同。吗啡增强了C57小鼠的奖励刺激，但拮抗DBA小鼠。与这些发现一致，在使用固定比率时间表在C57小鼠中有效的条件下，静脉内吗啡在DBA小鼠中不作为阳性应答剂，并且在渐进比率时间表下未能维持足以维持恒定药物摄入速率的应答水平。相比之下，安非他明增强大脑刺激的奖励效应在两种基因型中相似。这些发现提供了强有力的证据表明，吗啡是奖励的C57基因型，而不是在DBA基因型。考虑到这些基因型在候选基因鉴定和基因定位中的重要性，了解它们的相对易感性是重要的。
The C57BL/6J and DBA/2J mice are the most common genotypes used to identify chromosomal regions and neurochemical mechanisms of interest in opioid addiction. Unfortunately, outside of the oral two-bottle choice procedure, limited and sometimes controversial evidence is available for determining their relative sensitivity to the rewarding effects of morphine. The purpose of this study was to utilize classically accepted models of drug abuse liability to determine relative susceptibility to the rewarding effects of morphine. The ability of morphine or amphetamine to potentiate lateral hypothalamic brain stimulation and intravenous morphine self-administration (across three doses in a Fixed Ratio schedule and highest dose in Progressive Ratio schedules) was investigated in both genotypes In both measures, C57 and DBA mice differed dramatically in their response to morphine. Morphine potentiated rewarding stimulation in the C57 mice, but antagonized it in the DBA mice. Consistent with these findings, intravenous morphine did not serve as a positive reinforcer in DBA mice under conditions that were effective in the C57 mice using a Fixed Ratio schedule and failed to sustain levels of responding sufficient to maintain a constant rate of drug intake under a Progressive Ratio schedule. In contrast, amphetamine potentiated the rewarding effects of brain stimulation similarly in the two genotypes. These findings provide strong evidence that morphine is rewarding in the C57 genotype and not in the DBA genotype. Understanding their relative susceptibility is important given the prominence of these genotypes in candidate gene identification and gene mapping.
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影响因子：
3.4
作者：
ELMER, GI;PIEPER, JO;GEORGE, FR
通讯作者：
GEORGE, FR
影响因子：
5.3
作者：
Ford, CP;Mark, GP;Williams, JT
通讯作者：
Williams, JT
影响因子：
14.8
作者：
Carlezon, William A., Jr.;Chartoff, Elena H.
通讯作者：
Chartoff, Elena H.
影响因子：
2.9
作者：
CAZALA, P;CAZALS, Y;CARDO, B
通讯作者：
CARDO, B
影响因子：
5
作者：
ELMER, GI;EVANS, JL;CADET, JL
通讯作者：
CADET, JL