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














  • Molecular mechanisms of CNS synaptogenesis.

    abstract::Synapses of the mammalian CNS are asymmetric sites of cell-cell adhesion between nerve cells. They are designed to mediate the rapid and efficient transmission of signals from the presynaptic bouton of one neuron to the postsynaptic plasma membrane of a second neuron. Significant progress has been made in the characte...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Garner CC,Zhai RG,Gundelfinger ED,Ziv NE

    更新日期:2002-05-01 00:00:00

  • Aberrant Network Activity in Schizophrenia.

    abstract::Brain dynamic changes associated with schizophrenia are largely equivocal, with interpretation complicated by many factors, such as the presence of therapeutic agents and the complex nature of the syndrome itself. Evidence for a brain-wide change in individual network oscillations, shared by all patients, is largely e...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Hunt MJ,Kopell NJ,Traub RD,Whittington MA

    更新日期:2017-06-01 00:00:00

  • Language and the Construction of Time through Space.

    abstract::Speakers of different languages think about time differently in accordance with the spatial metaphors common in their languages. Furthermore, learning new spatial metaphors in language instills new non-linguistic representations of time, suggesting that language can play a causal role in constructing mental timelines....

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: Boroditsky L

    更新日期:2018-10-01 00:00:00

  • Sound localization and delay lines--do mammals fit the model?

    abstract::The current dominant model of binaural sound localization proposes that the lateral position of a sound source is determined by the position of maximal activation within an array of binaural coincidence-detector neurons that are tuned to different interaural time differences (ITDs). The tuning of a neuron for an ITD i...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: McAlpine D,Grothe B

    更新日期:2003-07-01 00:00:00

  • Noisy Synaptic Conductance: Bug or a Feature?

    abstract::More often than not, action potentials fail to trigger neurotransmitter release. And even when neurotransmitter is released, the resulting change in synaptic conductance is highly variable. Given the energetic cost of generating and propagating action potentials, and the importance of information transmission across s...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Rusakov DA,Savtchenko LP,Latham PE

    更新日期:2020-06-01 00:00:00

  • Ion Channel Functions in Early Brain Development.

    abstract::During prenatal brain development, ion channels are ubiquitous across several cell types, including progenitor cells and migrating neurons but their function has not been clear. In the past, ion channel dysfunction has been primarily studied in the context of postnatal, differentiated neurons that fire action potentia...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Smith RS,Walsh CA

    更新日期:2020-02-01 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

  • The reconstruction of cerebellar circuits.

    abstract::Repair of adult 'point-to-point' systems by neural grafting is possible only when grafted neurons succeed in synaptically replacing the host's missing neurons, thus re-establishing the anatomical and functional integrity of the impaired circuits. Grafting experiments carried out on the cerebellum of the adult pcd (Pur...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Sotelo C,Alvarado-Mallart RM

    更新日期:1991-08-01 00:00:00

  • Complement anaphylatoxin receptors on neurons: new tricks for old receptors?

    abstract::Activation of the complement system has been reported in a variety of inflammatory diseases and neurodegenerative processes of the CNS. Recent evidence indicates that complement proteins and receptors are synthesized on or by glial cells and, surprisingly, neurons. Among these proteins are the receptors for the chemot...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


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    更新日期:1999-09-01 00:00:00

  • Acid-sensing ion channels: advances, questions and therapeutic opportunities.

    abstract::Extracellular acid can have important effects on neuron function. In central and peripheral neurons, acid-sensing ion channels (ASICs) have emerged as key receptors for extracellular protons, and recent studies suggest diverse roles for these channels in the pathophysiology of pain, ischemic stroke and psychiatric dis...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Wemmie JA,Price MP,Welsh MJ

    更新日期:2006-10-01 00:00:00

  • The Circuit Motif as a Conceptual Tool for Multilevel Neuroscience.

    abstract::Modern neuroscientific techniques that specifically manipulate and measure neuronal activity in behaving animals now allow bridging of the gap from the cellular to the behavioral level. However, in doing so, they also pose new challenges. Research using incompletely defined manipulations in a high-dimensional space wi...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Braganza O,Beck H

    更新日期:2018-03-01 00:00:00

  • Sleep, clocks, and synaptic plasticity.

    abstract::Sleep is widely believed to play an essential role in synaptic plasticity. However, the precise mechanisms governing this presumptive function are largely unknown. There is also evidence for independent circadian oscillations in synaptic strength and morphology. Therefore, synaptic changes observed after sleep reflect...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Frank MG,Cantera R

    更新日期:2014-09-01 00:00:00

  • Advancing NMDA Receptor Physiology by Integrating Multiple Approaches.

    abstract::NMDA receptors (NMDARs) are ion channels activated by the excitatory neurotransmitter glutamate and are essential to all aspects of brain function, including learning and memory formation. Missense mutations distributed throughout NMDAR subunits have been associated with an array of neurological disorders. Recent stru...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Zhou HX,Wollmuth LP

    更新日期:2017-03-01 00:00:00

  • Mitochondrial synapses: intracellular communication and signal integration.

    abstract::Communication is a central theme in biology. Consequently, specialized structures have evolved to permit rapid communication among cells, tissues, organs, and physiological systems, thus enhancing the overall function and adaptation of the organism. A prime example is the neuronal synapse. In the brain, synaptic commu...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Picard M

    更新日期:2015-08-01 00:00:00

  • Kalirin and Trio: RhoGEFs in Synaptic Transmission, Plasticity, and Complex Brain Disorders.

    abstract::Changes in the actin cytoskeleton are a primary mechanism mediating the morphological and functional plasticity that underlies learning and memory. The synaptic Ras homologous (Rho) guanine nucleotide exchange factors (GEFs) Kalirin and Trio have emerged as central regulators of actin dynamics at the synapse. The incr...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Paskus JD,Herring BE,Roche KW

    更新日期:2020-07-01 00:00:00

  • Tools for investigating functional interactions between ligands and G-protein-coupled receptors.

    abstract::A general assay for evaluating functional interactions between ligands and G-protein-coupled receptors within minutes has been developed. The system uses the principles employed by animals such as reptiles, amphibians and fish to control their colors. In nature, activation of G-protein-coupled receptors expressed by s...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


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    更新日期:1994-04-01 00:00:00

  • Multiple sclerosis: novel perspectives on newly forming lesions.

    abstract::The mechanisms underlying lesion formation in multiple sclerosis are unknown. The prevailing view is that macrophages are primary mediators of myelin destruction in the relapsing and remitting forms of this disease. However, recent findings have revealed widespread oligodendrocyte apoptosis in the absence of a clear c...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


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  • Ca2+ and secretory-vesicle dynamics.

    abstract::Exocytosis in neurones and neuroendocrine cells is triggered by an increase in the cytosolic concentration of Ca2+, and is followed by endocytotic membrane retrieval. Electrophysiological studies have characterized the nature of the Ca2+ signal that is required for exocytosis, and have defined the Ca(2+)-dependent ste...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


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  • Development of whisker-related patterns in marsupials: factors controlling timing.

    abstract::In mature rodents, whisker-related patterns are known to be present in three levels of the brain: the brainstem trigeminal nuclei, the ventrobasal thalamus and the somatosensory cortex. These patterns have been demonstrated using neuroanatomical tracing techniques, histological and histochemical staining methods and e...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Waite PM,Marotte LR,Leamey CA,Mark RF

    更新日期:1998-06-01 00:00:00

  • Neuronal cell death in Huntington's disease: a potential role for dopamine.

    abstract::Huntington's disease is an inherited neurodegenerative disorder, the cause of which is unknown. Excitotoxicity, mitochondrial dysfunction and oxidative stress are all likely to contribute to the striatal cell death that occurs in this disorder. There are accumulating data indicating that under specific circumstances, ...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Jakel RJ,Maragos WF

    更新日期:2000-06-01 00:00:00

  • The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis?

    abstract::Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations ...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Fukui H,Moraes CT

    更新日期:2008-05-01 00:00:00

  • Glial cells aid axonal target selection.

    abstract::A key problem in developmental neurobiology is how axons home in on their correct target tissue and establish the correct synaptic contacts. Recent work shows that in the developing Drosophila visual system a population of distinct lamina glial cells ensures correct target layer selection of retinal axons. In the abse...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Pielage J,Klämbt C

    更新日期:2001-08-01 00:00:00

  • The pulvinar and visual salience.

    abstract::One of the major problems of living in a rich visual environment is deciding which particular object or location should be chosen for complete processing or attention; that is, deciding which object is most salient at any particular time. The pulvinar has enlarged substantially during evolution, although little has pr...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Robinson DL,Petersen SE

    更新日期:1992-04-01 00:00:00

  • The neurobiology of anhedonia and other reward-related deficits.

    abstract::Anhedonia, or markedly diminished interest or pleasure, is a hallmark symptom of major depression, schizophrenia and other neuropsychiatric disorders. Over the past three decades, the clinical definition of anhedonia has remained relatively unchanged, although cognitive psychology and behavioral neuroscience have expa...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Der-Avakian A,Markou A

    更新日期:2012-01-01 00:00:00

  • A rationale for the structure of color space.

    abstract::The colors perceived by humans in response to light stimuli are generally described in terms of four color categories (reds, greens, blues and yellows), the members of which are systematically arrayed around gray. This broadly accepted description of color sensation differs fundamentally from the light that induces it...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章,评审


    authors: Lotto RB,Purves D

    更新日期:2002-02-01 00:00:00

  • Neurobiology a century ago at the Marine Biological Laboratory, Woods Hole.

    abstract::Neurobiology was a central concern at the Marine Biological Laboratory (MBL), Woods Hole at the end of the last century, when the director Charles Otis Whitman set up a seminar for discussion of research and general issues in 'neurology', which took place annually from 1896 to 1900 and generated intense interest among...

    journal_title:Trends in neurosciences

    pub_type: 历史文章,杂志文章,评审


    authors: Maienschein J

    更新日期:1990-10-01 00:00:00

  • How does morphology relate to function in sensory arbors?

    abstract::Sensory dendrites fall into many different morphological and functional classes. Polymodal nociceptors are one subclass of sensory neurons, which are of particular note owing to their elaborate dendritic arbors. Complex developmental programs are required to form these arbors and there is striking conservation of morp...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: Hall DH,Treinin M

    更新日期:2011-09-01 00:00:00

  • Neuroethics: a modern context for ethics in neuroscience.

    abstract::Neuroethics, a recently modernized field at the intersection of bioethics and neuroscience, is founded on centuries of discussion of the ethical issues associated with mind and behavior. Broadly defined, neuroethics is concerned with ethical, legal and social policy implications of neuroscience, and with aspects of ne...

    journal_title:Trends in neurosciences

    pub_type: 历史文章,杂志文章,评审


    authors: Illes J,Bird SJ

    更新日期:2006-09-01 00:00:00

  • Chandelier Cells Illuminate Inhibitory Control of Prefrontal-Amygdala Outputs.

    abstract::Inhibitory interneurons comprise a diverse subpopulation of cells that are critical to circuit function. How distinct inhibitory microcircuits control long-range projections remains poorly understood. A recent study by Lu and colleagues uncovered a unidirectional microcircuit of prefrontal chandelier cells that prefer...

    journal_title:Trends in neurosciences

    pub_type: 评论,杂志文章


    authors: Giustino TF,Maren S

    更新日期:2017-11-01 00:00:00

  • The prairie vole: an emerging model organism for understanding the social brain.

    abstract::Unlike most mammalian species, the prairie vole is highly affiliative, forms enduring social bonds between mates and displays biparental behavior. Over two decades of research on this species has enhanced our understanding of the neurobiological basis not only of monogamy, social attachment and nurturing behaviors but...

    journal_title:Trends in neurosciences

    pub_type: 杂志文章


    authors: McGraw LA,Young LJ

    更新日期:2010-02-01 00:00:00