Neural bases for addictive properties of benzodiazepines

Kelly R. Tan, Matthew Brown, Gwenaël Labouébe, Cédric Yvon, Cyril Creton, Jean Marc Fritschy, Uwe Rudolph, Christian Lüscher

Research output: Contribution to journalArticlepeer-review

Abstract

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 behaviour. 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 (γ-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on α1-containing GABA A receptors 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 GABAA receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing α1 may be devoid of addiction liability.

Original languageEnglish (US)
Pages (from-to)769-774
Number of pages6
JournalNature
Volume463
Issue number7282
DOIs
StatePublished - Feb 11 2010
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Neural bases for addictive properties of benzodiazepines'. Together they form a unique fingerprint.

Cite this