什么樣的神經(jīng)機(jī)制可以解釋人體生理從消閑性藥物的消費(fèi)到強(qiáng)迫性濫用甚至毒癮復(fù)發(fā)的轉(zhuǎn)化,？一項(xiàng)發(fā)表在7月在線出版的《自然—神經(jīng)科學(xué)》期刊上的論文研究了這一過程，在神經(jīng)細(xì)胞的連接中,，研究人員發(fā)現(xiàn)了一些由谷氨酸受體所控制的可卡因?qū)е碌某志眯宰冃巍?/p>
可卡因等上癮性藥物會(huì)在大腦中留下可探測(cè)的印記,。特別的是，可卡因的使用改變了神經(jīng)細(xì)胞間的連接,，因此,，通過它們傳遞到其他神經(jīng)細(xì)胞的信號(hào)或被放大或被縮小，這一過程被稱為藥物引導(dǎo)突觸塑性,。
通過對(duì)模式小鼠進(jìn)行研究,，Christian Luscher和同事分析了藥物上癮所導(dǎo)致的神經(jīng)活性和行為的變化。在小鼠大腦中名為VTA的區(qū)域中,，他們發(fā)現(xiàn)可卡因所導(dǎo)致的神經(jīng)突觸塑性變化受谷胺酸受體mGluR1所調(diào)控,。控制VTA區(qū)域中mGluR1的活性可影響該區(qū)域突觸塑性的早期和持久性形成,，這一區(qū)域?qū)νＫ幒笮∈髮?duì)可卡因的尋求行為密切相關(guān),。阻斷VTA區(qū)域的變化可降低小鼠對(duì)可卡因的渴求行為。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
