Florey Neuroscience Institutes, University of Melbourne, Parkville, Vic., 3010, Australia.
Pharmacol Biochem Behav. 2012 Feb;100(4):811-24. doi: 10.1016/j.pbb.2011.03.015. Epub 2011 Apr 2.
Addiction is a chronic disorder characterised by repeated bouts of drug taking, abstinence and relapse. The addicted state may be in part due to drug-induced neuroadaptations in the mesocorticolimbic and corticostriatal pathways. Recently focus has been on the role of aberrant glutamate transmission and its contribution to the hierarchical control over these systems. This review will expand our current knowledge of the most recent advances that have been made in preclinical animal models that provide evidence that implicate metabotropic glutamate receptors (mGluRs) in contributing to the neuroadaptations pertinent to addiction, as well as the role of Homer proteins in regulating these responses. The recent discovery of receptor mosaics will be discussed which add an additional dimension to the complexity of understanding the mechanism of glutamate mediated behaviours. Finally this review introduces a new area related to glutamatergic responses, namely microRNAs, that may become pivotal in directing our future understanding of how to best target intervention strategies to prevent addictive behaviours.
成瘾是一种慢性疾病,其特征是反复出现药物滥用、戒断和复发。成瘾状态可能部分归因于中脑边缘和皮质纹状体通路中的药物诱导的神经适应性改变。最近,人们关注的焦点是异常谷氨酸传递及其对这些系统的分层控制的贡献。这篇综述将扩展我们对最近在临床前动物模型中取得的进展的了解,这些模型提供了证据,表明代谢型谷氨酸受体(mGluRs)有助于与成瘾相关的神经适应性,以及 Homer 蛋白在调节这些反应中的作用。最近发现的受体镶嵌现象将增加对理解谷氨酸介导行为机制的复杂性的另一个维度。最后,本综述介绍了与谷氨酸能反应相关的一个新领域,即 microRNAs,这可能对指导我们未来理解如何最好地针对干预策略以防止成瘾行为至关重要。