什么样的神经机制可以解释人体生理从消闲性药物的消费到强迫性滥用甚至毒瘾复发的转化？一项发表在7月在线出版的《自然—神经科学》期刊上的论文研究了这一过程，在神经细胞的连接中，研究人员发现了一些由谷氨酸受体所控制的可卡因导致的持久性变形。
可卡因等上瘾性药物会在大脑中留下可探测的印记。特别的是，可卡因的使用改变了神经细胞间的连接，因此，通过它们传递到其他神经细胞的信号或被放大或被缩小，这一过程被称为药物引导突触塑性。
通过对模式小鼠进行研究，Christian Luscher和同事分析了药物上瘾所导致的神经活性和行为的变化。在小鼠大脑中名为VTA的区域中，他们发现可卡因所导致的神经突触塑性变化受谷胺酸受体mGluR1所调控。控制VTA区域中mGluR1的活性可影响该区域突触塑性的早期和持久性形成，这一区域对停药后小鼠对可卡因的寻求行为密切相关。阻断VTA区域的变化可降低小鼠对可卡因的渴求行为。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Neuroscience 12, 1036 - 1041 (2009)13 July 2009 | doi:10.1038/nn.2367
Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc
Manuel Mameli1, Briac Halbout2, Cyril Creton1, David Engblom3, Jan Rodriguez Parkitna3, Rainer Spanagel2 & Christian Lüscher1,4,5
Abstract
Addictive drugs hijack mechanisms of learning and memory that normally underlie reinforcement of natural rewards and induce synaptic plasticity of glutamatergic transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor–dependent synaptic plasticity in DA neurons, whereas plasticity in the nucleus accumbens (NAc) occurs only after repeated injections. Whether these two forms of plasticity are independent or hierarchically organized remains unknown. We combined ex vivo electrophysiology in acute brain slices with behavioral assays modeling drug relapse in mice and found that the duration of the cocaine-evoked synaptic plasticity in the VTA is gated by mGluR1. Overriding mGluR1 in vivo made the potentiation in the VTA persistent. This led to synaptic plasticity in the NAc, which contributes to cocaine-seeking behavior after protracted withdrawal. Impaired mGluR1 function in vulnerable individuals could represent a first step in the recruitment of the neuronal network that underlies drug addiction.
1 Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland.
2 Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
3 Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
4 Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.
5 Geneva Neuroscience Center, Geneva, Switzerland.
