Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake.
Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake.
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DOI：
10.1016/j.biopsych.2009.09.016
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发表时间：
2010-05-01
影响因子：
10.6
通讯作者：
Hodge, Clyde W.
中科院分区：
文献类型：
--
作者：
Besheer, Joyce;Grondin, Julie J. M.;Cannady, Reginald;Sharko, Amanda C.;Faccidomo, Sara;Hodge, Clyde W.
关键词：
I组和II组代谢型谷氨酸受体（mGluRs）的系统性调节在多种动物模型中调控乙醇自我给药。尽管这些受体在与奖赏相关的脑区表达，但它们在乙醇自我给药中功能参与的解剖学特异性仍有待确定。本研究旨在评估I组（mGluR5）和II组（mGluR2/3）在中脑边缘皮质脑区在乙醇自我给药中的功能作用。
嗜酒（P）大鼠是一种高饮酒量的遗传模型，在操作条件反射箱中被训练自行摄取乙醇（15%体积比）和水。然后评估了脑特定部位注射mGluR5拮抗剂2 - 甲基 - 6 -（苯乙炔基）吡啶盐酸盐（MPEP）和mGluR2/3激动剂对自我给药维持的影响。
在伏隔核微量注射mGluR5拮抗剂MPEP在不改变运动活性的剂量下减少了乙醇自我给药。相比之下，在伏隔核注射mGluR2/3激动剂LY379268减少了自我给药，并导致运动活性非特异性降低。mGluR5的作用显示出解剖学特异性，因为在背内侧尾状核或内侧前额叶皮质注射MPEP对乙醇自我给药没有影响。为了确定强化物特异性，P大鼠被训练自行摄取蔗糖（0.4%重量比）和水，并测试了伏隔核内注射MPEP的效果。MPEP没有改变蔗糖自我给药或运动行为。
这些结果表明，在具有高饮酒遗传风险的个体中，伏隔核中特定的mGluR5活性是维持乙醇自我给药所必需的。
Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized. This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration. Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration. Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity. The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior. These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption.
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影响因子：
7.6
作者：
Besheer, J;Hodge, CW
通讯作者：
Hodge, CW
影响因子：
3.4
作者：
BURNS, LH;EVERITT, BJ;ROBBINS, TW
通讯作者：
ROBBINS, TW
影响因子：
5.3
作者：
Baptista, MAS;Martin-Fardon, R;Weiss, F
通讯作者：
Weiss, F
DOI：
10.1124/jpet.105.090449
发表时间：
2005-11-01
影响因子：
3.5
作者：
Cowen, MS;Djouma, E;Lawrence, AJ
通讯作者：
Lawrence, AJ
DOI：
10.1523/jneurosci.2366-09.2009
发表时间：
2009-07-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Besheer J;Grondin JJ;Salling MC;Spanos M;Stevenson RA;Hodge CW
通讯作者：
Hodge CW