The mGlu5 receptor regulates extinction of cocaine-driven behaviours
The mGlu5 receptor regulates extinction of cocaine-driven behaviours
复制标题
DOI：
10.1016/j.drugalcdep.2014.01.017
复制
发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Lawrence, Andrew J.
中科院分区：
文献类型：
--
作者：
Bird, Michael K.;Lohmann, Peter;Lawrence, Andrew J.
背景资料：有大量的证据表明，代谢型谷氨酸5（mGlu 5）受体在addiction-related behaviors.Methods方面：在这里，我们使用了一个很好的特点线mGlu 5-缺陷小鼠进一步研究可卡因驱动的行为，这种受体的作用。我们证实了以前报道的赤字海马长时程增强和相关的空间学习impairment.Results：尽管空间学习缺陷，mGlu 5缺陷小鼠开发和保持条件性的位置偏好可卡因，这表明可卡因奖励和巴甫洛夫条件是完整的，在这些动物。然而，值得注意的是，与野生型同窝小鼠相比，mGlu 5缺陷小鼠在可卡因条件位置偏好的消失方面表现出明显的缺陷。此外，在一个固定的比例操作性静脉内自我管理的范例，两种基因型表现出类似的响应可卡因在两个不同的剂量，而mGlu 5缺陷型小鼠表现出增强响应的渐进比例时间表。此外，线索诱导的药物寻求禁欲后被夸大mGlu 5-缺陷mice.Conclusion：总的来说，这些研究结果表明，虽然mGlu 5受体可能参与介导可卡因的奖励作用，它似乎是必要的可卡因驱动的行为的灭绝。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Background: There is extensive evidence implicating the metabotropic glutamate 5 (mGlu5) receptor in aspects of addiction-related behaviours.Methods: Here, we used a well-characterized line of mGlu5-deficient mice to further examine the role of this receptor in cocaine-driven behaviours. We confirmed the previously reported deficit in hippocampal long-term potentiation and associated spatial learning impairment.Results: Despite a spatial learning deficit, mGlu5-deficient mice developed and maintained a conditioned place preference to cocaine, suggesting cocaine reward and Pavlovian conditioning are intact in these animals. Notably, however, mGlu5-deficient mice exhibited a marked deficit in the extinction of a cocaine-conditioned place preference compared to wild type littermates. Moreover, in a fixed ratio operant intravenous self-administration paradigm, both genotypes showed similar responding for cocaine over two different doses, while mGlu5-deficient mice displayed enhanced responding on a progressive ratio schedule. In addition, cue-induced drug-seeking after abstinence was exaggerated in mGlu5-deficient mice.Conclusion: Collectively, these findings suggest that while the mGlu5 receptor may be involved in mediating the rewarding effects of cocaine, it appears necessary for the extinction of cocaine-driven behaviours. (C) 2014 Elsevier Ireland Ltd. All rights reserved.