miRNAs与药物成瘾

药物成瘾是一种慢性复发性脑病,主要表现为不可控制的对药物持续渴求和戒断后的高复吸。目前观点认为,成瘾是中脑腹侧被盖（ventral tegmental area,VTA）到伏隔核（nucleus accumbens,NAc）脑区多巴胺能奖赏通路中神经可塑性发生改变而导致的一种神经精神疾病。基因表达变化在神经可塑性中发挥着重要作用,但成瘾药物导致相关脑区结构和功能改变的机制还不甚清楚。微小RNAs（microRNAs,miRNAs）是一类非编码RNA,主要通过结合靶基因mRNA 3′非翻译区（3′untranslated region,3′UTR）,在转录后水平阻断其翻译成蛋白质或触发其不稳定而降解。越来越多的研究证实,miRNAs参与调节成瘾相关神经可塑性的变化。本文较系统地阐述miRNAs在药物成瘾中的作用研究进展,将为深入阐明药物成瘾的机制以及药物成瘾临床有效干预和诊治提供新思路。     

毒品成瘾的分子基础

毒品成瘾的形成是一个循序渐进的、综合性的过程。在此过程,机体在分子、细胞学水平发生了代偿性变化,进而导致成瘾的一系列症状。中脑边缘系统多巴胺系统的激活是多种毒品成瘾的共同神经生物学特点。长期地施用毒品,可以导致机体的功能系统发生变化,即耐受性、依赖性、敏化性。上述不同的功能变化特点有其相应的分子细胞学基础。     

药物成瘾的蛋白质组学研究

药物成瘾涉及脑内多种蛋白含量、结构及功能的复杂改变,主要涉及代谢酶类、细胞骨架蛋白、分子伴侣、细胞内信号途径相关蛋白、突触功能相关蛋白和氧化还原相关蛋白等类型。蛋白质组学能对生理与病理状态下的体液、组织或细胞中基因组编码的所有蛋白质组分进行高通量的综合分析,针对筛选出的有意义“候选”蛋白（candidate protein）进行深入验证研究,不仅可能从蛋白质水平上阐明成瘾的神经生物学作用机制,还有助于建立诊断标准,发现抗成瘾药物治疗的潜在靶点。     

Acupuncture for the Treatment of Drug Addiction

Over the last three decades there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. Wen of Hong Kong was the first (1972) to report that acupuncture at 4 body points and 2 ear points combined with electrical stimulation can relieve opioid withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the USA, who finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of drug abuse. The recent advance in this field was made by Dr. Han of the Peking University, Beijing, who characterized a protocol (2005), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and prevent relapse of heroin use. In this review, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed. Special issue article in honor of Dr. Ji-Sheng Han.     

针刺治疗药物成瘾的研究进展

近35年来,针刺治疗物质依赖的研究引起了越来越多的国内外相关学者和临床医生的关注.该领域内的研究进展大致可以分为三个主要阶段:(一)香港的温祥来医师于1973年首次报道,采用电针(两对体针和一对耳针连接电刺激)可以减轻阿片成瘾者的戒断症状(身体依赖);(二)纽约M.Smith医师(1985)领导的美国国家针刺脱毒协会(NADA)确定,仅采用耳针,不加电刺激,治疗药物依赖(身体依赖);(三)北京大学神经科学研究所(PKU NRI)韩济生教授及其同事(1992-)用特定频率的躯体穴位电刺激缓解海洛因成瘾者的戒断症状(身体依赖),并可抑制患者脱毒后对毒品的心理渴求(精神依赖)以预防复吸.本文将综述针刺干预药物依赖的临床疗效、实验研究及初步作用机制.     

Glutamate and Brain Glutaminases in Drug Addiction

Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.