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Neural bases for addictive properties of benzodiazepines

Tan, Kelly R. and Brown, Matthew and Labouèbe, Gwenaël and Yvon, Cédric and Creton, Cyril and Fritschy, Jean-Marc and Rudolph, Uwe and Lüscher, Christian. (2010) Neural bases for addictive properties of benzodiazepines. Nature, 463 (7282). pp. 769-774.

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Official URL: http://edoc.unibas.ch/50651/

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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) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha1-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 alpha1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction liability.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Physiopathology of basal ganglia neuronal subcircuits (Tan)
UniBasel Contributors:Tan, Kelly
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Macmillan
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Nov 2017 11:06
Deposited On:29 Nov 2017 11:06

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