前边缘皮质中谷氨酸受体在阿片类药物成瘾中的作用

阿片类药物是临床上广泛使用的镇痛药物,但其成瘾性也一直是临床难以解决的问题。阿片类药物成瘾的具体机制仍不十分清楚。研究发现,前边缘皮质与环境偶联的药物成瘾密切相关。本文综述近年来前边缘皮质谷氨酸受体在阿片类药物成瘾过程中的作用研究,为进一步探究阿片类药物成瘾的机制,寻找阿片类药物成瘾的防治新靶点提供参考。     

中枢神经系统ERK信号通路在药物成瘾中的作用机制研究进展

药物成瘾是一种慢性复发性脑病。反复的药物暴露可引起脑环路产生神经适应性变化,导致强迫性觅药行为以及复吸。有许多研究发现,生物体内细胞间的信号转导级联放大通路介导的中枢神经系统奖赏环路的重塑,以及成瘾相关的学习和记忆的神经可塑性改变是药物成瘾的重要分子机制。研究表明细胞外调节激酶(extracellular signal-regulatedkinase,ERK)与药物成瘾引起的神经适应性、奖赏效应和觅药行为的复吸直接相关。因此,该文就ERK在药物成瘾中的作用机制做系统的综述。药物成瘾中ERK信号通路作用机制的研究将为深入理解药物成瘾的分子调控机制提供重要的理论基础,并为临床药物成瘾和复吸的治疗提供新的分子靶标和新的策略。     

CREB参与慢性应用吗啡引起的神经元和突触的可塑性和适应性

反复应用阿片类药物,机体启动适应机制,神经元及突触功能产生适应性改变,导致神经元及神经网络功能发生长期改变,是机体形成药物依赖和耐受的机制之一[1]。目前研究认为,阿片和其他成瘾药物具有共同的细胞和解剖通路,而受体后细胞、突触和神经网络的适应性改变是成瘾形成的关键[1]。阿片类药物与其受体结合后,     

近年来戒毒药物的研究进展

目的对近年来戒毒药物的研究进展作一综述。方法查阅近年来国内外公开发表的有关研究论文 ,按戒毒药物的作用靶点分类汇总。结果与结论目前戒毒药物的作用靶点主要包括阿片受体、α2 受体、DA2 受体、M受体、NMDA受体以及钙离子通道等 ,与此相对应的戒毒药物均具有较好的疗效。寻找有效的成瘾药物治疗的作用靶点以及在分子水平上研制新的戒毒药物是目前此类工作的研究方向     

阿片类药物成瘾者执行功能的研究进展

执行功能在阿片成瘾的形成、维持、戒治与复发中都具有重要作用。长期慢性的阿片类药物滥用会导致成瘾者的执行功能普遍受到损伤,继而影响药物成瘾的戒治与复发。本文梳理了近年来阿片类药物在神经心理学、事件相关电位以及影像学等领域的执行功能相关研究结果,以期为我国的阿片类药物成瘾的戒治工作提供来自认知神经科学的科学依据。     

抗阿片成瘾药物研究历史与现状

阿片成瘾是一种慢性复发性脑疾病,临床症状包括躯体依赖、稽延症状、精神依赖和复吸, 治疗的关键是防复吸。防复吸药物的研究包括以阿片受体和非阿片受体为靶标的药物。代表性药物分别为阿片受体激动剂美沙酮和受体阻断剂纳屈酮,新型阿片受体配体噻吩诺啡能够完全阻断吗啡等阿片类药物引起的躯体和精神依赖,防止阿片复吸。研究表明,参与调节阿片精神依赖和复吸的非阿片受体作用系统包括多巴胺受体、兴奋性氨基酸受体、γ-氨基丁酸受体、乙酰胆碱受体、5-HT受体、CB1受体和神经营养因子受体等。多巴胺D3受体阻断剂Y-QA14自身无致成瘾性,同时具有抗可卡因和海洛因成瘾及防复吸的作用。咪唑啉Ⅰ型受体激动剂胍丁胺具有抗阿片躯体和精神依赖、缓解稽延症状和防复吸的作用,机制与激活咪唑啉Ⅰ型受体后减轻阿片受体、多巴胺系统和谷氨酸系统的代偿性适应用关。本文将就阿片、阿片成瘾生物学基础、防阿片复吸药物研发展、作用机制、历史、现状和发展趋势加以综述。     

药物成瘾治疗新动向

阿片类药物成瘾防复吸一直是作为困扰世界医学界的主题,目前临床上采用阿片类受体激动剂美沙酮、半激动半拮抗剂丁丙喏啡梯度递减替代治疗方案,阿片类药物导致的躯体依赖已经得以解决,临床脱毒基本完成。但吸毒患者复吸率依然很高,导致复吸的因素很多,主要是稽延性症状、心瘾及环境因素,针对复吸原因,许多科研人员正投入大量的工作以研究防复吸的新途径。本文主要介绍药物成瘾治疗的一些新动向。1 阿片类药物受体拮抗剂纳曲酮的应用纳曲酮为纯阿片受体拮抗剂,通过阻断外源性阿片类物质与阿片受体结合,抑制阿片类药物对阿片受体的强化作用,从…     

电压依赖性钙通道与阿片类药物成瘾之间的关系

阿片类药物成瘾属慢性复发性脑病,主要表现为对成瘾性药物的强迫用药行为及用药量的不可控制性,其机制复杂,治疗困难,复发率高,因此对阿片类药物依赖戒断的机制及治疗的研究一直是医学界关注的热点和难点.大量研究证明电压依赖性钙通道（voltage dependent calcium channels,VDCCs）与阿片类药物成瘾的形成之间存在着密切的关系,VDCCs可通过多种途径参与阿片成瘾的形成.并且临床上,多种钙拮抗剂治疗吗啡戒断综合征也取得了一定的疗效,间接证明了VDCCs与阿片成瘾的形成之间存在着密切的关系.现对VDCCs与阿片类药物成瘾之间的关系综述如下.     

NO-cGMP信息通路在阿片类药物耐受和依赖中的调节作用

ＮＯ合酶抑制剂能阻断或逆转μ、δ激动剂耐受和戒断反应,而对κ激动剂无明显作用,其药理效应类似于阿片成瘾治疗的常用药物可乐定。甲基兰抑制鸟苷酸环化酶活性,使ｃＧＭＰ生成减少,对阿片类药物耐受和戒断症状均有阻断作用,提示ＮＯ ｃＧＭＰ通路在阿片耐受和依赖发生中起重要作用,为寻找和设计治疗阿片类耐受成瘾的药物提供新的策略。     

miRNAs在甲基苯丙胺成瘾中的作用研究进展

甲基苯丙胺(methamphetamine,METH)成瘾是机体长期接触METH后,中枢神经系统在分子、细胞、神经环路功能和脑结构等层次发生的代偿性适应,该过程有多种途径和多种机制共同参与。miRNAs作为一种新型基因转录后调控分子和突触的调节因子,大量存在于中枢神经系统,对中枢神经系统具有重要的调控作用。研究表明,miRNAs在METH成瘾中发挥着重要的调控作用。该文对miRNAs在METH成瘾机制中的表达特征及调控作用进行综述,并将与METH成瘾相关的miRNAs分子以及各miRNAs分子在不同组织器官中的差异性表达部位进行归纳整理,为进一步研究miRNAs分子在METH成瘾中的作用及发现新的药物作用靶点提供参考。     

Addiction and withdrawal--current views.

The final common pathway of addiction (the dopamine hypothesis of reward) has recently been evolving, with the mesocorticolimbic dopaminergic system now seen as key to natural rewards and drug-seeking behaviour, though perhaps having less of a role in the maintenance of such behaviour. The perception of a common pathway has meant that treatments for one drug of addiction have 'crossed-over' and become possible treatments for other addictive drugs.     

Integration of generalized vulnerability to drug and alcohol addiction

Summary

The vulnerability to develop addiction to alcohol has been well established in familial and genetic studies. Similar familial and genetic studies have supported a vulnerability to drug addiction. The co‐occurrence of alcohol and drug addiction in the same individuals is highly prevalent in clinical populations. Common putative neurochemical mechanisms underlie addiction to both alcohol and drugs, namely, in the mesolimbic pathway and the locus ceruleus in the brain. Treatment strategies are directed at both alcohol and multiple drug addictions in patient populations. The formulation of a generalized vulnerability that extends to both alcohol and drug addiction is not only possible but necessary to explain the substantial numbers of individuals who develop both alcohol and drug addictions. Future research that is pertinent and relevant may depend on the understanding of a generalized vulnerability to develop alcohol and drug addiction and its application in diagnostic strategies and treatment models.     

The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction

Rationale

Love has long been referred to as an addiction in literature and poetry. Scientists have often made comparisons between social attachment processes and drug addiction, and it has been suggested that the two may share a common neurobiological mechanism. Brain systems that evolved to govern attachments between parents and children and between monogamous partners may be the targets of drugs of abuse and serve as the basis for addiction processes.

Objectives

Here, we review research on drug addiction in parallel with research on social attachments, including parent–offspring attachments and social bonds between mating partners. This review focuses on the brain regions and neurochemicals with the greatest overlap between addiction and attachment and, in particular, the mesolimbic dopamine (DA) pathway.

Results

Significant overlap exists between these two behavioral processes. In addition to conceptual overlap in symptomatology, there is a strong commonality between the two domains regarding the roles and sites of action of DA, opioids, and corticotropin-releasing factor. The neuropeptides oxytocin and vasopressin are hypothesized to integrate social information into attachment processes that is not present in drug addiction.

Conclusions

Social attachment may be understood as a behavioral addiction, whereby the subject becomes addicted to another individual and the cues that predict social reward. Understandings from both fields may enlighten future research on addiction and attachment processes.     

The neurocircuitry of addiction: an overview

Drug addiction presents as a chronic relapsing disorder characterized by persistent drug-seeking and drug-taking behaviours. Given the significant detrimental effects of this disease both socially and economically, a considerable amount of research has been dedicated to understanding a number of issues in addiction, including behavioural and neuropharmacological factors that contribute to the development, loss of control and persistence of compulsive addictive behaviours. In this review, we will give a broad overview of various theories of addiction, animal models of addiction and relapse, drugs of abuse, and the neurobiology of drug dependence and relapse. Although drugs of abuse possess diverse neuropharmacological profiles, activation of the mesocorticolimbic system, particularly the ventral tegmental area, nucleus accumbens, amygdala and prefrontal cortex via dopaminergic and glutamatergic pathways, constitutes a common pathway by which various drugs of abuse mediate their acute reinforcing effects. However, long-term neuroadaptations in this circuitry likely underlie the transition to drug dependence and cycles of relapse. As further elucidated in more comprehensive reviews of various subtopics on addiction in later sections of this special issue, it is anticipated that continued basic neuroscience research will aid in the development of effective therapeutic interventions for the long-term treatment of drug-dependent individuals.     

New perspectives in the studies on endocannabinoid and cannabis: a role for the endocannabinoid-arachidonic acid pathway in drug reward and long-lasting relapse to drug taking

Growing evidence on the involvement of cannabinoids in the rewarding effects of various kinds of drugs of abuse has suggested that not only the classical dopaminergic and opioidergic, but also the most recently established endocannabinoid system is implicated in the brain reward system. Furthermore, the interplay between the three systems has been shown to be an essential neural substrate underlying many aspects of drug addiction including craving and relapse. Relapse, the resumption of drug taking following a period of drug abstinence, is considered the main hurdle in treating drug addiction. Yet, little is known about its underlying mechanisms. The link between the endocannabinoid system and the arachidonic cascade is currently being clarified. While several findings have, indeed, shown the essential role of the endocannabinoid system in the reinstatement model, the endocannabinoid-arachidonic acid pathway may also be an important part in the neural machinery underlying relapse. This evidence may provide an alternative approach that will open a novel strategy in combating drug addiction.     

Common Neural Adaptations and Bidirectional Influences of Stress and Addiction

Abstract

Objective: Clinical evidence suggests a complex-per-haps correlative-relationship between stressful experiences and addiction. The goal of this review is to provide an overview of recent basic research linking stress and addiction, to indicate novel areas of study, and to suggest how data from basic research may influence clinical assessment and treatment of patients with stress-related disorders, substance abuse, or a history of both disorders.

Methods: Reviewed here are recent basic research (preclinical) articles available via PubMed (www.ncbi.nlm.nih.gov) with particular relevance to novel neural mechanisms underlying the putative stress/addiction relationship.

Findings: Three types of relationships between stress and addiction are identified and discussed: (1) Neural adaptations common to both chronic stress and chronic exposure to drugs of abuse; (2) The influence of stress on the rewarding or sensitizing aspects of drugs of abuse; and (3) The influence of stress on the relapse to drug taking after a drug-free period. Each relationship appears to involve alterations in dopaminergic and glutamatergic systems and their related second messenger pathways. However, brain regions that influence the brain's reward pathway, such as the hippocampus, and other novel aspects of neuroplasticity, such as adult neurogenesis, are also receiving attention.

Conclusions: A wealth of evidence shows that stress and addiction can produce similar adaptations in discrete brain regions, and that there is bidirectional influence of the experience of stress and drug exposure. These preclinical findings encourage further exploration of the neural mechanisms underlying stress and addiction with the hope that additional discoveries will aid treatment of patients with stress-related disorders and addiction, or comorbid diagnoses.     

Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine

There is strong evidence for the existence of Gq/11-coupled dopamine receptors in the brain but the mechanism by which dopamine signaling activates Gq/11, or its roles in neuronal function, are only just beginning to be understood. The importance of such a pathway is underlined by putative links between dopamine-regulated phosphoinositide signaling and several central nervous system disorders that include schizophrenia, addiction and Parkinson's disease.     

Offspring of alcoholics have enhanced antagonistic placebo response

In this study, 85 college-age men who reported normal drinking practices believed they were drinking malt liquor when they actually drank dealcoholized beer. Following drinking, 11 subjects with an alcoholic biological father showed a significantly larger heart rate decrease (p less than .05) than subjects with a nonalcoholic father. The results are discussed in terms of opponent process and classical conditioning theories of addiction, and the etiological pathway from risk factor to final manifestation of alcoholism.     

Neuroplasticity in the mesolimbic dopamine system and cocaine addiction

The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.