2013年10月10日 訊 /生物谷BIOON/ --近日，科研人員發(fā)現(xiàn)了大腦的一組神經(jīng)元可能通過(guò)在戒煙期間增加對(duì)尼古丁的響應(yīng)從而破壞戒煙的努力,。
此前的研究已經(jīng)證明了尼古丁與大腦中的尼古丁乙酰膽堿受體（nAChRs）結(jié)合,，隨著時(shí)間的推移，持續(xù)的結(jié)合可能改變神經(jīng)回路從而促進(jìn)成癮,。尼古丁乙酰膽堿受體（nAChRs）的α3,、β4和α5亞單位在重尼古丁使用和復(fù)吸方面起到了關(guān)鍵的作用。Ines Iba,？ez-Tallon及其同事研究了小鼠在戒斷尼古丁期間的這些亞單位和調(diào)控尼古丁渴求的神經(jīng)信號(hào)之間的相互作用,。這組作者比較了來(lái)自這些小鼠中系帶——這是α3、β4和α5受體亞單位聚集的一個(gè)大腦區(qū)域——的兩個(gè)區(qū)域的神經(jīng)元,，并且發(fā)現(xiàn)了促進(jìn)大腦有節(jié)奏的電脈沖的所謂節(jié)律通道的存在,。破壞這些節(jié)律器讓從未接觸過(guò)尼古丁的小鼠誘導(dǎo)產(chǎn)生了尼古丁戒斷的癥狀。
進(jìn)一步的分析表明尼古丁激活了含有α3,、β4的尼古丁乙酰膽堿受體（nAChRs）從而增強(qiáng)未接觸尼古丁的小鼠的節(jié)律器活動(dòng),。盡管這類(lèi)活動(dòng)也在接觸尼古丁的小鼠身上觀察到了，這組作者報(bào)告說(shuō),，當(dāng)接觸過(guò)尼古丁的小鼠進(jìn)行尼古丁戒斷并且重新接觸尼古丁的時(shí)候,，節(jié)律器活動(dòng)增加到了原來(lái)的兩倍以上。這組作者說(shuō),，這些發(fā)現(xiàn)識(shí)別出了大腦的一組神經(jīng)元,，它們?cè)谝欢螘r(shí)間的戒斷之后對(duì)尼古丁做出了不同的響應(yīng),，這提示這些神經(jīng)元活動(dòng)的改變可能使戒煙變得困難,。(生物谷Bioon.com)
生物谷推薦英文原文：
PNAS doi：10.1073/pnas.1313103110
Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons
Andreas G rlicha， Beatriz Antolin-Fontes,， Jessica L. Ables,， Silke Frahm， Marta A. limak,， Joseph D. Dougherty,， and Inés Ib ez-Tallon
The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula–interpeduncular axis as a critical relay circuit in the control of nicotine dependence. Although clear roles for α3， β4,， and α5 receptors in nicotine aversion and withdrawal have been established,， the cellular and molecular mechanisms that participate in signaling nicotine use and contribute to relapse have not been identified. Here， using translating ribosome affinity purification (TRAP) profiling,， electrophysiology,， and behavior， we demonstrate that cholinergic neurons,， but not peptidergic neurons,， of the medial habenula (MHb) display spontaneous tonic firing of 2–10 Hz generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist ZD7288 in the habenula precipitates somatic and affective signs of withdrawal. Further， we show that a strong， α3β4-dependent increase in firing frequency is observed in these pacemaker neurons upon acute exposure to nicotine. No change in the basal or nicotine-induced firing was observed in cholinergic MHb neurons from mice chronically treated with nicotine. We observe,， however,， that， during withdrawal,， reexposure to nicotine doubles the frequency of pacemaking activity in these neurons. These findings demonstrate that the pacemaking mechanism of cholinergic MHb neurons controls withdrawal,， suggesting that the heightened nicotine sensitivity of these neurons during withdrawal may contribute to smoking relapse.
