Hooked on benzodiazepines: GABAA receptor subtypes and addiction.


:Benzodiazepines are widely used clinically to treat anxiety and insomnia. They also induce muscle relaxation, control epileptic seizures, and can produce amnesia. Moreover, benzodiazepines are often abused after chronic clinical treatment and also for recreational purposes. Within weeks, tolerance to the pharmacological effects can develop as a sign of dependence. In vulnerable individuals with compulsive drug use, addiction will be diagnosed. Here we review recent observations from animal models regarding the cellular and molecular basis that might underlie the addictive properties of benzodiazepines. These data reveal how benzodiazepines, acting through specific GABA(A) receptor subtypes, activate midbrain dopamine neurons, and how this could hijack the mesolimbic reward system. Such findings have important implications for the future design of benzodiazepines with reduced or even absent addiction liability.


Trends Neurosci


Trends in neurosciences


Tan KR,Rudolph U,Lüscher C




Has Abstract


2011-04-01 00:00:00














  • The developmental origins of spatial navigation: are we headed in the right direction?

    abstract::Navigation depends upon neural systems that monitor spatial location and head orientation. Recent developmental findings have led some to conclude that these systems are innate. Such claims are premature. But also, there are more meaningful ways to arrive at answers about developmental origins than by invoking the out...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Blumberg MS

    更新日期:2015-02-01 00:00:00

  • Synaptic vesicle endocytosis: fast and slow modes of membrane retrieval.

    abstract::Several modes of synaptic vesicle release, retrieval and recycling have been identified. In a well-established mode of exocytosis, termed 'full-collapse fusion', vesicles empty their neurotransmitter content fully into the synaptic cleft by flattening out and becoming part of the presynaptic membrane. The fused vesicl...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Smith SM,Renden R,von Gersdorff H

    更新日期:2008-11-01 00:00:00

  • Serotonin: a regulator of neuronal morphology and circuitry.

    abstract::Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms whereby serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulator...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Daubert EA,Condron BG

    更新日期:2010-09-01 00:00:00

  • Friends and foes in synaptic transmission: the role of tomosyn in vesicle priming.

    abstract::Priming is the process by which vesicles become available for fusion at nerve terminals and is modulated by numerous proteins and second messengers. One of the prominent members of this diverse family is tomosyn. Tomosyn has been identified as a syntaxin-binding protein; it inhibits vesicle priming, but its mode of ac...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Ashery U,Bielopolski N,Barak B,Yizhar O

    更新日期:2009-05-01 00:00:00

  • P2X receptors bring new structure to ligand-gated ion channels.

    abstract::P2X receptors are cation-selective ion channels that open on binding to extracellular ATP; they play a role in fast synaptic transmission between neurones, and from autonomic nerves to smooth muscles. Isolation of cDNAs that encode P2X receptors in the smooth muscle of vas deferens and in phaeochromocytoma cells indic...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Surprenant A,Buell G,North RA

    更新日期:1995-05-01 00:00:00

  • Ion channel organization of the myelinated fiber.

    abstract::The myelinated axon provides a model in which it is possible to examine how various types of ion channels are incorporated into a membrane to form an excitable neuronal process. The available evidence now indicates that mammalian myelinated fibers contain a repertoire of physiologically active membrane molecules inclu...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Black JA,Kocsis JD,Waxman SG

    更新日期:1990-02-01 00:00:00

  • Neural mechanisms for prediction: do insects have forward models?

    abstract::'Forward models' are increasingly recognized as a crucial explanatory concept in vertebrate motor control. The essential idea is that an important function implemented by nervous systems is prediction of the sensory consequences of action. This is often associated with higher cognitive capabilities; however, many of t...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Webb B

    更新日期:2004-05-01 00:00:00

  • Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity.

    abstract::The ability of neurons to modulate the strength of their synaptic connections has been shown to depend on the relative timing of pre- and postsynaptic action potentials. This form of synaptic plasticity, called spike-timing-dependent plasticity (STDP), has become an attractive model for learning at the single-cell lev...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Kampa BM,Letzkus JJ,Stuart GJ

    更新日期:2007-09-01 00:00:00

  • Synaptic Receptor Diversity Revealed Across Space and Time.

    abstract::In their 1994 paper, Monyer et al. described unique functional properties and cell type-specific expression of NMDA receptor (NMDAR) GluN2 subunits, suggesting that the roles of NMDAR vary across brain regions and throughout development. This influential work not only provided insight into how molecular diversity impa...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: Swanger SA,Traynelis SF

    更新日期:2018-08-01 00:00:00

  • MeCP2 as an Activator of Gene Expression.

    abstract::Rett syndrome is a neurodevelopmental disorder that primarily affects females and is caused by mutations in the methyl-CpG-binding-protein 2 (MECP2) gene. Initially, MeCP2 had been shown to be a repressor of gene transcription. In their 2008 paper, Chahrour and colleagues (DOI: 10.1126/science.1153252) reported that M...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Horvath PM,Monteggia LM

    更新日期:2018-02-01 00:00:00

  • Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson's Disease.

    abstract::The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endoph...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Nguyen M,Wong YC,Ysselstein D,Severino A,Krainc D

    更新日期:2019-02-01 00:00:00

  • Adding fuel to the fire: the impact of stress on the ageing brain.

    abstract::Both ageing and chronic stress are associated with altered brain plasticity, dysregulation of the immune system, and an increased risk of developing brain disorders; all of which have consequences for cognitive and emotional processing. Here we examine the similarities between behavioural changes during ageing and str...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Prenderville JA,Kennedy PJ,Dinan TG,Cryan JF

    更新日期:2015-01-01 00:00:00

  • Long-range interactions in visual perception.

    abstract::Classical receptive-field concepts have been used to explain local perceptual effects such as border contrast and Mach bands, but are not sufficient to explain global perceptual effects. Examples are the perception of illusory contours, area contrast, color constancy, depth planes, coherent motion and texture contrast...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Spillmann L,Werner JS

    更新日期:1996-10-01 00:00:00

  • Stress and Seizures: Space, Time and Hippocampal Circuits.

    abstract::Stress is a major trigger of seizures in people with epilepsy. Exposure to stress results in the release of several stress mediators throughout the brain, including the hippocampus, a region sensitive to stress and prone to seizures. Stress mediators interact with their respective receptors to produce distinct effects...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Gunn BG,Baram TZ

    更新日期:2017-11-01 00:00:00

  • A vitamin for the brain.

    abstract::In the central nervous system (CNS) the function of retinoic acid, the active metabolite of vitamin A, is best understood from its action in guiding embryonic development; as development comes to completion, retinoic acid signaling declines. However, it is increasingly recognized that this signaling mechanism does not...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Shearer KD,Stoney PN,Morgan PJ,McCaffery PJ

    更新日期:2012-12-01 00:00:00

  • Genetic mouse models for studying inhibitors of spinal axon regeneration.

    abstract::The laboratory mouse has emerged as a primary model organism for studying axon regeneration after experimental spinal cord injury, owing to its genetic amenability. Mutant mouse models are contributing significantly to our understanding of the molecular mechanisms of axon regeneration failure in the adult mammalian ce...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Zheng B,Lee JK,Xie F

    更新日期:2006-11-01 00:00:00

  • The behaving brain of a fly.

    abstract::The use of Drosophila as a suitable system to answer behavioural questions is usually based on the availability of mutant phenotypes. Indeed, the 'single-gene' approach to behaviour was a very illuminating strategy in practical and conceptual terms, and served to prove that the genetic mechanisms sustaining behaviour ...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: Ferrús A,Canal I

    更新日期:1994-11-01 00:00:00

  • Hippocampal neurogenesis and forgetting.

    abstract::The hippocampus is thought to automatically encode all experience, yet the vast majority of our experiences are not remembered later. Although psychological theories have postulated the existence of decay processes for declarative memory, the corresponding neurobiological mechanisms are unknown. Here we develop the hy...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Frankland PW,Köhler S,Josselyn SA

    更新日期:2013-09-01 00:00:00

  • Calcium and polyphosphoinositide control of cytoskeletal dynamics.

    abstract::Dynamic alterations in the structure of the neuronal cytoskeleton are necessary for axonal growth and guidance during development and may also be involved in modulation of synaptic function. Recent evidence suggests that the structural and mechanochemical properties of the cytoskeletal protein, actin, are critical to ...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Forscher P

    更新日期:1989-11-01 00:00:00

  • Similarities between actions of estrogen and BDNF in the hippocampus: coincidence or clue?

    abstract::The principal ovarian estrogen, estradiol, and brain-derived neurotrophic factor (BDNF) have widespread effects on the CNS that have usually been studied independently. This article examines the similarities in the effects of estradiol and BDNF in the hippocampus, in light of the evidence that estradiol can induce BDN...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Scharfman HE,Maclusky NJ

    更新日期:2005-02-01 00:00:00

  • Regulation of neuronal function by calcium.

    abstract::In the classical picture of brain function, electrical impulses are initiated in sensory organs and spread rapidly down axons, jumping synaptic clefts by neurochemical transmission. Patterns of electrical activity generated in this way integrate information throughout the brain and result in coordinated motor output. ...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Kennedy MB

    更新日期:1989-11-01 00:00:00

  • Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but imperfect.

    abstract::Genetic mouse models based on identification of genes that cause Huntington's and Parkinson's diseases have revolutionized understanding of the mechanistic pathophysiological progression of these disorders. These models allow the earliest manifestations of the diseases to be identified, and they display behavioral, ne...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Levine MS,Cepeda C,Hickey MA,Fleming SM,Chesselet MF

    更新日期:2004-11-01 00:00:00

  • Free radicals and aging.

    abstract::Aging is characterized by decrements in maximum function and accumulation of mitochondrial DNA mutations, which are best observed in organs such as the brain that contain post-mitotic cells. Oxygen radicals are increasingly considered responsible for part of these aging changes. Comparative studies of animals with dif...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Barja G

    更新日期:2004-10-01 00:00:00

  • Direct regulation of ion channels by fatty acids.

    abstract::A variety of fatty acids regulate the activity of specific ion channels by mechanisms not involving the enzymatic pathways that convert arachidonic acid to oxygenated metabolites. Furthermore, these actions of fatty acids occur in patches of membrane excised from the cell and are not mediated by cellular signal transd...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Ordway RW,Singer JJ,Walsh JV Jr

    更新日期:1991-03-01 00:00:00

  • Brain Circuits Encoding Reward from Pain Relief.

    abstract::Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the h...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Navratilova E,Atcherley CW,Porreca F

    更新日期:2015-11-01 00:00:00

  • Localization of brain function using magnetic resonance imaging.

    abstract::When nuclear magnetic resonance images (MRIs) of the brain are acquired in rapid succession they exhibit small differences in signal intensity in positions corresponding to focal areas of activation. These signal changes result from small differences in the magnetic resonance signal caused by variations in the oxygena...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Cohen MS,Bookheimer SY

    更新日期:1994-07-01 00:00:00

  • Cognitive consonance: complex brain functions in the fruit fly and its relatives.

    abstract::The fruit fly, Drosophila melanogaster, has become a model for the study of a growing number of human characteristics because of the power of its genetics. Higher cognitive functions, however, might be assumed to be out of reach for the little fly. But the cumulative history of cognitive studies in insects and some of...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: Greenspan RJ,van Swinderen B

    更新日期:2004-12-01 00:00:00

  • Control of gap-junctional communication in astrocytic networks.

    abstract::Astrocytes, which constitute the most abundant cell type in mammalian brain, are extensively coupled to one another through gap junctions composed mainly of connexin43. In regions exhibiting high levels of connexin43 expression, tens of astrocytes are labeled following single-cell intracellular injection. Importantly,...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Giaume C,McCarthy KD

    更新日期:1996-08-01 00:00:00

  • The monoaminergic innervation of the cerebral cortex is not diffuse and nonspecific.

    abstract::It is generally thought that monoamines play a nonspecific role in modulating cortical activity. However, several lines of evidence now indicate that cortical monoaminergic afferents show remarkable anatomical specificity. In particular, there is unequivocal evidence for regional, laminar and intracortical specificity...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Parnavelas JG,Papadopoulos GC

    更新日期:1989-09-01 00:00:00

  • Interneuron Diversity series: Rhythm and mood in perisomatic inhibition.

    abstract::GABAergic interneurons innervating the perisomatic region of pyramidal cells control population discharge patterns, and thereby all cognitive operations in the cerebral cortex. A striking dichotomy in the function of this interneuron population seems to emerge from the synthesis of recent molecular, anatomical and ele...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Freund TF

    更新日期:2003-09-01 00:00:00