药物成瘾相关的神经结构可塑性改变

不计后果的药物渴求和滥用是药物成瘾的一个显著特征。药物滥用可以诱导行为学和心理学持续性改变的发生,这些持续性改变由相关神经通路(尤其是奖赏系统)神经结构的可塑性变化所引起。本文综述了安非他明、可卡因、尼古丁和吗啡等药物诱发的相关脑区的神经可塑性改变以及引起这些改变的可能原因。药物成瘾诱发的神经结构可塑性改变反映了相关神经系统突触连接的重塑,这些重塑改变该系统的功能,由此便产生了药物滥用的一系列后遗症状———包括成瘾。     

The Path to Enlightenment： Making Sense of Genomic and Proteomic Information

Whereas genomics describes the study of genome, mainly represented by its gene expression on the DNA or RNA level, the term proteomics denotes the study of the proteome, which is the protein complement encoded by the genome. In recent years, the number of proteomic experiments increased tremendously. While all fields of proteomics have made major technological advances, the biggest step was seen in bioinformatics. Biological information management relies on sequence and structure databases and powerful software tools to translate experimental results into meaningful biological hypotheses and answers. In this resource article, I provide a collection of databases and software available on the Internet that are useful to interpret genomic and proteomic data. The article is a toolbox for researchers who have genomic or proteomic datasets and need to put their findings into a biological context.     

生命科学数据库BIOSIS Previews信息资源的查询

生命科学数据库BIOSIS Previews是科技人员有效地利用Internet网络查找国外生命科学信息的世界著名数据库。本文对如何利用BIOSIS Previews查询生命科学相关学术文献作了介绍。     

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。     

Bis-azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation

A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked dopamine release. The preliminary structure–activity relationships of these new analogues suggest that bPiDDB binds in an extended conformation at the nAChR binding site, and that flexibility of the linker may be important for its high potency in inhibiting nAChRs mediating nicotine-evoked dopamine release.     

Systems genetics of sensation seeking

Sensation seeking is a multifaceted, heritable trait which predicts the development of substance use and abuse in humans; similar phenomena have been observed in rodents. Genetic correlations among sensation seeking and substance use indicate shared biological mechanisms, but the genes and networks underlying these relationships remain elusive. Here, we used a systems genetics approach in the BXD recombinant inbred mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking. Using the operant sensation seeking (OSS) paradigm, we quantified preference for sensory stimuli in 120 male and 127 female mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We used relative preference for the active and inactive levers to dissociate preference for sensory stimuli from locomotion and exploration phenotypes. We identified genomic regions on chromosome 4 (155.236‐155.742 Mb) and chromosome 13 (72.969‐89.423 Mb) associated with distinct behavioral components of OSS. Using publicly available behavioral data and mRNA expression data from brain regions involved in reward processing, we identified (a) genes within these behavioral QTL exhibiting genome‐wide significant cis‐eQTL and (b) genetic correlations among OSS phenotypes, ethanol phenotypes and mRNA expression. From these analyses, we nominated positional candidates for behavioral QTL associated with distinct OSS phenotypes including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression, preference for sensory stimuli and multiple ethanol phenotypes suggest that heritable variation in Gnb1 expression in reward circuitry partially underlies the widely reported relationship between sensation seeking and substance use.     

Depression‐like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake

Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression‐like symptoms during early periods of withdrawal, compared with non‐binge users. The impact of varying durations of MA abstinence on depression‐like symptoms and on subsequent MA intake was examined in mice genetically prone to binge‐level MA consumption. Binge‐level MA intake was induced using a multiple‐bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression‐like symptoms were measured using a tail‐suspension test and a subsequent forced‐swim test, after forced abstinence of 6 and 30 hours from a 28‐day course of chronic MA intake. An additional study measured the same depression‐like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression‐like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug‐naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression‐like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression‐like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.     

Internet‐delivered psychological treatments: from innovation to implementation

Internet interventions, and in particular Internet‐delivered cognitive behaviour therapy (ICBT), have existed for at least 20 years. Here we review the treatment approach and the evidence base, arguing that ICBT can be viewed as a vehicle for innovation. ICBT has been developed and tested for several psychiatric and somatic conditions, and direct comparative studies suggest that therapist‐guided ICBT is more effective than a waiting list for anxiety disorders and depression, and tends to be as effective as face‐to‐face CBT. Studies on the possible harmful effects of ICBT are also reviewed: a significant minority of people do experience negative effects, although rates of deterioration appear similar to those reported for face‐to‐face treatments and lower than for control conditions. We further review studies on change mechanisms and conclude that few, if any, consistent moderators and mediators of change have been identified. A recent trend to focus on knowledge acquisition is considered, and a discussion on the possibilities and hurdles of implementing ICBT is presented. The latter includes findings suggesting that attitudes toward ICBT may not be as positive as when using modern information technology as an adjunct to face‐to‐face therapy (i.e., blended treatment). Finally, we discuss future directions, including the role played by technology and machine learning, blended treatment, adaptation of treatment for minorities and non‐Western settings, other therapeutic approaches than ICBT (including Internet‐delivered psychodynamic and interpersonal psychotherapy as well as acceptance and commitment therapy), emerging regulations, and the importance of reporting failed trials.     

Focus: Addiction: Video Game Use in the Treatment of Amblyopia: Weighing the Risks of Addiction

Video games have surged in popularity due to their entertainment factor and, with recent innovation, their use in health care. This review explores the dual facets of video games in treating vision impairment in amblyopia as well as their potential for overuse and addiction. Specifically, this review examines video game addiction from a biopsychosocial perspective and relates the addictive qualities of video games with their use as a therapeutic treatment for amblyopia. Current literature supports both the identification of video game addiction as a disease, as well as the therapeutic potential of video games in clinical trials. We show the need for clinicians to be aware of the dangers associated with video game overuse and the need for future studies to examine the risks associated with their health care benefits.     

Against Anonymity

In ‘New Threats to Academic Freedom’ 1 1 Minerva, F. . New Threats to Academic Freedom . Bioethics 2013 ; DOI: 10.1111/bioe.12066 .
Francesca Minerva argues that anonymity for the authors of controversial articles is a prerequisite for academic freedom in the Internet age. This argument draws its intellectual and emotional power from the author's account of the reaction to the on‐line publication of ‘ After‐birth abortion: why should the baby live?’ 2 2 Giubilini, A. & Minerva, F. . After‐birth Abortion. Why Should the Baby Live? J Med Ethics 2013 ; 39 : 261 – 263 .
– an article that provoked cascades of hostile postings and e‐mails. Reflecting on these events, Minerva proposes that publishers should offer the authors of controversial articles the option of publishing their articles anonymously. This response reviews the history of anonymous publication and concludes that its reintroduction in the Internet era would recreate problems similar to those that led print journals to abandon the practice: corruption of scholarly discourse by invective and hate speech, masked conflicts of interest, and a diminution of editorial accountability. It also contends that Minerva misreads the intent of the hostile e‐mails provoked by ‘After‐birth abortion,’ and that ethicists who publish controversial articles should take responsibility by dialoguing with their critics – even those whose critiques are emotionally charged and hostile.