近日，國際著名雜志Nature最新一期刊登了國外研究人員的最新研究成果“Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour,。”,，文章中，作者表示可卡因效應(yīng)是可逆轉(zhuǎn)的,。
突觸彈性已知會(huì)在藥物上癮中出現(xiàn),，但幾乎沒有證據(jù)將由藥物激發(fā)的彈性與在藥物上癮的動(dòng)物中所看到的行為適應(yīng)性聯(lián)系起來。Pascoli等人報(bào)告,，表達(dá)I-型多巴胺受體的“多巴胺能神經(jīng)元”中的特定“增強(qiáng)作用”（potentiation）,，會(huì)引起經(jīng)常是在暴露于可卡因的動(dòng)物中所觀察到的運(yùn)動(dòng)敏感性增強(qiáng)效應(yīng)。利用光遺傳學(xué)手段對(duì)這一通道實(shí)施的特定“去增強(qiáng)作用”（depotentiation）,，既會(huì)恢復(fù)正常突觸傳輸,，又會(huì)消除行為表現(xiàn)型。這些數(shù)據(jù)將“表達(dá)D1R的神經(jīng)元”的突觸“增強(qiáng)作用”與由藥物激發(fā)的行為聯(lián)系了起來,，并且說明,，由可卡因誘導(dǎo)的適應(yīng)性突觸變化的治療性逆轉(zhuǎn)可能會(huì)導(dǎo)致行為糾正。（生物谷Bioon.com）
doi:10.1038/nature10709
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Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour
Vincent Pascoli, Marc Turiault & Christian Lüscher
Drug-evoked synaptic plasticity is observed at many synapses and may underlie behavioural adaptations in addiction1. Mechanistic investigations start with the identification of the molecular drug targets. Cocaine, for example, exerts its reinforcing2 and early neuroadaptive effects3 by inhibiting the dopamine transporter, thus causing a strong increase in mesolimbic dopamine. Among the many signalling pathways subsequently engaged, phosphorylation of the extracellular signal-regulated kinase (ERK) in the nucleus accumbens4 is of particular interest because it has been implicated in NMDA-receptor and type 1 dopamine (D1)-receptor-dependent synaptic potentiation5 as well as in several behavioural adaptations6, 7, 8. A causal link between drug-evoked plasticity at identified synapses and behavioural adaptations, however, is missing, and the benefits of restoring baseline transmission have yet to be demonstrated. Here we find that cocaine potentiates excitatory transmission in D1-receptor-expressing medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time course that parallels locomotor sensitization. Depotentiation of cortical nucleus accumbens inputs by optogenetic stimulation in vivo efficiently restored normal transmission and abolished cocaine-induced locomotor sensitization. These findings establish synaptic potentiation selectively in D1R-MSNs as a mechanism underlying a core component of addiction, probably by creating an imbalance between distinct populations of MSNs in the nucleus accumbens. Our data also provide proof of principle that reversal of cocaine-evoked synaptic plasticity can treat behavioural alterations caused by addictive drugs and may inspire novel therapeutic approaches involving deep brain stimulation or transcranial magnetic stimulation.
