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Neural bases for addictive properties of benzodiazepines

Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathologic...

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Autores principales: Tan, Kelly R., Brown, Matthew, Labouèbe, Gwenaël, Yvon, Cédric, Creton, Cyril, Fritschy, Jean-Marc, Rudolph, Uwe, Lüscher, Christian
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871668/
https://www.ncbi.nlm.nih.gov/pubmed/20148031
http://dx.doi.org/10.1038/nature08758
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author Tan, Kelly R.
Brown, Matthew
Labouèbe, Gwenaël
Yvon, Cédric
Creton, Cyril
Fritschy, Jean-Marc
Rudolph, Uwe
Lüscher, Christian
author_facet Tan, Kelly R.
Brown, Matthew
Labouèbe, Gwenaël
Yvon, Cédric
Creton, Cyril
Fritschy, Jean-Marc
Rudolph, Uwe
Lüscher, Christian
author_sort Tan, Kelly R.
collection PubMed
description Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behavior. The neural basis for the addictive nature of benzodiazepines however remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) receptors in nearby interneurons. Such disinhibition, which relies on α1-containing GABA(A)Rs expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell type-specific expression of α1-containing GABA(A)Rs in the ventral tegmental area. The data also suggest that subunitselective benzodiazepines sparing α1 may be devoid of addiction liability.
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spelling pubmed-28716682010-08-11 Neural bases for addictive properties of benzodiazepines Tan, Kelly R. Brown, Matthew Labouèbe, Gwenaël Yvon, Cédric Creton, Cyril Fritschy, Jean-Marc Rudolph, Uwe Lüscher, Christian Nature Article Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behavior. The neural basis for the addictive nature of benzodiazepines however remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) receptors in nearby interneurons. Such disinhibition, which relies on α1-containing GABA(A)Rs expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell type-specific expression of α1-containing GABA(A)Rs in the ventral tegmental area. The data also suggest that subunitselective benzodiazepines sparing α1 may be devoid of addiction liability. 2010-02-11 /pmc/articles/PMC2871668/ /pubmed/20148031 http://dx.doi.org/10.1038/nature08758 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Tan, Kelly R.
Brown, Matthew
Labouèbe, Gwenaël
Yvon, Cédric
Creton, Cyril
Fritschy, Jean-Marc
Rudolph, Uwe
Lüscher, Christian
Neural bases for addictive properties of benzodiazepines
title Neural bases for addictive properties of benzodiazepines
title_full Neural bases for addictive properties of benzodiazepines
title_fullStr Neural bases for addictive properties of benzodiazepines
title_full_unstemmed Neural bases for addictive properties of benzodiazepines
title_short Neural bases for addictive properties of benzodiazepines
title_sort neural bases for addictive properties of benzodiazepines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871668/
https://www.ncbi.nlm.nih.gov/pubmed/20148031
http://dx.doi.org/10.1038/nature08758
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