Opiate versus psychostimulant addiction: the differences do matter

The publication of the psychomotor stimulant theory of addiction in 1987 and the finding that addictive drugs increase dopamine concentrations in the rat mesolimbic system in 1988 have led to a predominance of psychobiological theories that consider addiction to opiates and addiction to psychostimulants as essentially identical phenomena. Indeed, current theories of addiction - hedonic allostasis, incentive sensitization, aberrant learning and frontostriatal dysfunction - all argue for a unitary account of drug addiction. This view is challenged by behavioural, cognitive and neurobiological findings in laboratory animals and humans. Here, we argue that opiate addiction and psychostimulant addiction are behaviourally and neurobiologically distinct and that the differences have important implications for addiction treatment, addiction theories and future research.     

药物成瘾及成瘾记忆的研究现状

本文在介绍药物成瘾与学习和记忆密切相关的神经回路及共同分子机制的基础上,围绕学习和记忆在药物成瘾中的作用,综述了关联性学习与复吸,关联性学习与敏化,异常关联性学习与强迫性用药行为,关联性学习及成瘾记忆与成瘾,多重记忆系统与成瘾的发生发展等方面的研究进展,并强调了突触可塑性及成瘾记忆在药物成瘾中的重要性。在此基础上提出：作为慢性脑病的药物成瘾的形成过程的重要特征是它包含着信息的特殊学习类型。药物成瘾与依赖于多巴胺的关联性学习紊乱有密切关系。海马可能在成瘾中扮演重要角色。     

Focus: Addiction: Methodological and Conceptual Limitations in Exercise Addiction Research

The aim of this brief analytical review is to highlight and disentangle research dilemmas in the field of exercise addiction. Research examining exercise addiction is primarily based on self-reports, obtained by questionnaires (incorporating psychometrically validated instruments), and interviews, which provide a range of risk scores rather than diagnosis. Survey methodology indicates that the prevalence of risk for exercise addiction is approximately 3 percent among the exercising population. Several studies have reported a substantially greater prevalence of risk for exercise addiction in elite athletes compared to those who exercise for leisure. However, elite athletes may assign a different interpretation to the assessment tools than leisure exercisers. The present paper examines the: 1) discrepancies in the classification of exercise addiction; 2) inconsistent reporting of exercise addiction prevalence; and 3) varied interpretation of exercise addiction diagnostic tools. It is concluded that there is the need for consistent terminology, to follow-up results derived from exercise addiction instruments with interviews, and to follow a theory-driven rationale in this area of research.     

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Despite substantial evidence for sex differences in addiction epidemiology, addiction‐relevant behaviors and associated neurobiological phenomena, the mechanisms and implications of these differences remain unknown. Genetic analysis in model organism is a potentially powerful and effective means of discovering the mechanisms that underlie sex differences in addiction. Human genetic studies are beginning to show precise risk variants that influence the mechanisms of addiction but typically lack sufficient power or neurobiological mechanistic access, particularly for the discovery of the mechanisms that underlie sex differences. Our thesis in this review is that genetic variation in model organisms are a promising approach that can complement these investigations to show the biological mechanisms that underlie sex differences in addiction.     

Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

In this review we propose that there are sex differences in how men and women enter onto the path that can lead to addiction. Males are more likely than females to engage in risky behaviors that include experimenting with drugs of abuse, and in susceptible individuals, they are drawn into the spiral that can eventually lead to addiction. Women and girls are more likely to begin taking drugs as self-medication to reduce stress or alleviate depression. For this reason women enter into the downward spiral further along the path to addiction, and so transition to addiction more rapidly. We propose that this sex difference is due, at least in part, to sex differences in the organization of the neural systems responsible for motivation and addiction. Additionally, we suggest that sex differences in these systems and their functioning are accentuated with addiction. In the current review we discuss historical, cultural, social and biological bases for sex differences in addiction with an emphasis on sex differences in the neurotransmitter systems that are implicated.     

Review. The incentive sensitization theory of addiction: some current issues

We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation (‘wanting’) for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?     

内感受对成瘾行为的诱导及其岛叶的调控机制

内感受是机体对自身生理状态的感觉.近年来,越来越多的研究证据表明,内感受可以调控成瘾行为,岛叶是其发挥作用的重要神经基础之一.目前,对岛叶作用机制的研究正受到高度重视.本文从岛叶的基本结构和功能出发,结合近几年来岛叶调控成瘾行为、行为抑制以及情感决策的重要发现,讨论岛叶在成瘾发生及发展过程中的可能作用及其机制,并根据已有的实验证据,试图提出较为合理的研究展望,以推动相关神经环路和神经化学机制研究的深入.     

食物成瘾及其神经环路调控机制

食物成瘾是指人们对某些特定食物（高度加工、可口、高热量的食物）的依赖性达到难以控制的程度,并表现出一系列成瘾样的行为学变化,具有强迫性、长期性和反复性的特点。食物成瘾可引起肥胖症,而且是大部分人不能维持减肥效果或坚持限制性饮食以保持健康体重的核心因素。深入理解食物成瘾及其神经生物学机制,将为干预食物成瘾以改善肥胖提供准确的靶点。食物成瘾的诊断标准是耶鲁大学食物成瘾量表,而食物成瘾的动物模型为小鼠食物自我管理模型。外侧下丘脑-腹侧被盖区-伏隔核神经环路、腹侧被盖区-前边缘皮质-伏隔核神经环路和外侧隔核-结节核神经环路是调控食物成瘾的关键神经环路机制。     

Experimental genetic approaches to addiction

Drugs of abuse are able to elicit compulsive drug-seeking behaviors upon repeated administration, which ultimately leads to the phenomenon of addiction. Evidence indicates that the susceptibility to develop addiction is influenced by sources of reinforcement, variable neuroadaptive mechanisms, and neurochemical changes that together lead to altered homeostasis of the brain reward system. Addiction is hypothesized to be a cycle of progressive dysregulation of the brain reward system that results in the compulsive use and loss of control over drug taking and the initiation of behaviors associated with drug seeking. The view that addiction represents a pathological state of reward provides an approach to identifying the factors that contribute to vulnerability, addiction, and relapse in genetic animal models.     

Pathways and Networks-Based Analysis of Candidate Genes Associated with Nicotine Addiction

Nicotine is the addictive substance in tobacco and it has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unclear. Under such situation, a comprehensive analysis focusing on the overall functional characteristics of these genes, as well as how they interact with each other will provide us valuable information to understand nicotine addiction. In this study, we presented a systematic analysis on nicotine addiction-related genes to identify the major underlying biological themes. Functional analysis revealed that biological processes and biochemical pathways related to neurodevelopment, immune system and metabolism were significantly enriched in the nicotine addiction-related genes. By extracting the nicotine addiction-specific subnetwork, a number of novel genes associated with addiction were identified. Moreover, we constructed a schematic molecular network for nicotine addiction via integrating the pathways and network, providing an intuitional view to understand the development of nicotine addiction. Pathway and network analysis indicated that the biological processes related to nicotine addiction were complex. Results from our work may have important implications for understanding the molecular mechanism underlying nicotine addiction.     

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。     

Precursor or sequela: pathological disorders in people with Internet addiction disorder

Background

This study aimed to evaluate the roles of pathological disorders in Internet addiction disorder and identify the pathological problems in IAD, as well as explore the mental status of Internet addicts prior to addiction, including the pathological traits that may trigger Internet addiction disorder.

Methods and Findings

59 students were measured by Symptom CheckList-90 before and after they became addicted to the Internet. A comparison of collected data from Symptom Checklist-90 before Internet addiction and the data collected after Internet addiction illustrated the roles of pathological disorders among people with Internet addiction disorder. The obsessive-compulsive dimension was found abnormal before they became addicted to the Internet. After their addiction, significantly higher scores were observed for dimensions on depression, anxiety, hostility, interpersonal sensitivity, and psychoticism, suggesting that these were outcomes of Internet addiction disorder. Dimensions on somatisation, paranoid ideation, and phobic anxiety did not change during the study period, signifying that these dimensions are not related to Internet addiction disorder.

Conclusions

We can not find a solid pathological predictor for Internet addiction disorder. Internet addiction disorder may bring some pathological problems to the addicts in some ways.     

Approche cognitivo-comportementale de l’addiction à la cocaïne

Cocaine addiction has medical, psychological, cognitive, social, and legal consequences. For a while confined to a targeted audience, epidemiological data show that cocaine addiction considerably “increases” in Europe and reaches all social categories, including socialized people. The cognitive-behavioral approach provides a conceptual frame allowing a better understanding of the mechanisms involved in at the beginning and all along the cocaine addiction. Consumption and addiction to cocaine are then considered learned behaviors. Cognitive-behavioral therapies applied to the treatment of cocaine addiction include different therapeutic techniques that modify maladjusted behaviors, thoughts, and feelings leading to consumption. On a pharmacologic point of view, there is no drug treatment for this disorder, even though promising tracks emerged, especially the N-acétylcystéine.     

Focus: Personalized Medicine: Precision in Addiction Care: Does It Make a Difference?

This perspective article explores the possibilities of precision in addiction care — even better individually fitted or tailor-made care — and examines what changes we need to make in order to realize sensible progress in epidemiological key figures. The first part gives a short review on the development of addiction care and tries to answer the question of where we stand now and what has been achieved in addiction science through the development and evaluation of interventions in the past decades. Following this analysis, attention will be paid to what lies ahead. This second part focuses on the question of how addiction care can deal with the consequences of the emerging paradigm of personalized or precision medicine, which is based on the fundamental assumption that individual differences matter. Finally, some limitations and conditions as well as tasks and goals for progress are raised. In conclusion, it is argued that integration of addiction care in (mental) health care in the future is desirable.     

阿司匹林可抑制吗啡引起的HT22 细胞Wnt通路的激活

目的:研究阿司匹林对吗啡引起的Wnt通路的上调的影响。方法:在大鼠海马神经元元细胞系HT22细胞上建立了慢性吗啡成瘾模型,然后运用免疫荧光技术和Western blot技术检测wnt通路中β-catenin蛋白的表达变化变化,同时应用报告基因技术检测Wnt通路下游转录因子的活性。结果:在慢性吗啡成瘾模型组,β-catenin蛋白的表达显著增加,而在接受了6 h的阿司匹林预处理的慢性吗啡成瘾模型组,β-catenin蛋白的表达受到了显著的抑制。结论:阿司匹林可抑制吗啡引起的Wnt/β-catenin通路水平的过表达。     

Impulsivity, compulsivity, and top-down cognitive control

Impulsivity is the tendency to act prematurely without foresight. Behavioral and neurobiological analysis of this construct, with evidence from both animal and human studies, defines several dissociable forms depending on distinct cortico-striatal substrates. One form of impulsivity depends on the temporal discounting of reward, another on motor or response disinhibition. Impulsivity is commonly associated with addiction to drugs from different pharmacological classes, but its causal role in human addiction is unclear. We characterize in neurobehavioral and neurochemical terms a rodent model of impulsivity based on premature responding in an attentional task. Evidence is surveyed that high impulsivity on this task precedes the escalation subsequently of cocaine self-administration behavior, and also a tendency toward compulsive cocaine-seeking and to relapse. These results indicate that the vulnerability to stimulant addiction may depend on an impulsivity endophenotype. Implications of these findings for the etiology, development, and treatment of drug addiction are considered.     

Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction.

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the mu opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitization and endocytosis of receptors. Here, we demonstrate that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties. Moreover, this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of our understanding of the role of receptor endocytosis in the biology of opiate drug action and addiction.     

药物成瘾中的神经细胞骨架

神经细胞骨架对神经元功能有重要作用。药物成瘾会导致神经细胞病态发生,几乎在所有药物成瘾的蛋白质组学的研究中都能检测到细胞骨架蛋白的变化,细胞骨架蛋白在这个过程涉及神经细胞结构、突触可塑性、信号转导、功能蛋白的降解或修饰以及能量代谢等方面。本文综述了神经细胞骨架在药物成瘾中的研究。     

Nicotine and hippocampus-dependent learning

Addiction is a complex disorder because many factors contribute to the development and maintenance of addiction. One factor is learning. For example, drug-context associations that develop during drug use could facilitate drug craving upon re-exposure to contexts previously associated with drugs. Additionally, deficits in cognitive processes associated with withdrawal could precipitate relapse in attempts to ameliorate those deficits. Because addiction and learning involve common neural areas and cell signaling cascades, addiction-related changes in processes underlying plasticity may contribute to addiction. This article examines similarities between addiction and learning at the behavioral, neural, and cellular levels, with emphasis on the neural substrates underlying the effects of acute nicotine, chronic nicotine, and withdrawal from chronic nicotine on hippocampus-dependent contextual, learning.     

The Experience of Addiction as Told by the Addicted: Incorporating Biological Understandings into Self-Story

How do the addicted view addiction against the framework of formal theories that attempt to explain the condition? In this empirical paper, we report on the lived experience of addiction based on 63 semi-structured, open-ended interviews with individuals in treatment for alcohol and nicotine abuse at five sites in Minnesota. Using qualitative analysis, we identified four themes that provide insights into understanding how people who are addicted view their addiction, with particular emphasis on the biological model. More than half of our sample articulated a biological understanding of addiction as a disease. Themes did not cluster by addictive substance used; however, biological understandings of addiction did cluster by treatment center. Biological understandings have the potential to become dominant narratives of addiction in the current era. Though the desire for a ??unified theory?? of addiction seems curiously seductive to scholars, it lacks utility. Conceptual ??disarray?? may actually reflect a more accurate representation of the illness as told by those who live with it. For practitioners in the field of addiction, we suggest the practice of narrative medicine with its ethic of negative capability as a useful approach for interpreting and relating to diverse experiences of disease and illness.