Neural bases for addictive properties of benzodiazepines
Kelly R. Tan1, Matthew Brown1,6, Gwenaël Labouèbe1,6, Cédric Yvon1,6, Cyril Creton1, Jean-Marc Fritschy2, Uwe Rudolph3 & Christian Lüscher1,4,5
1. Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland
2. Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland
3. Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts 02478, USA
4. Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, CH-1211 Geneva, Switzerland
5. Geneva Neuroscience Center, CH-1211 Geneva, Switzerland
6. These authors contributed equally to this work.
Correspondence to: Christian Lüscher1,4,5 Correspondence and requests for materials should be addressed to C.L. (Email:
christian.luscher@unige.ch).
Top of page
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 GABAA (γ-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on α1-containing GABAA 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.
1. Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland
2. Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland
3. Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts 02478, USA
4. Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, CH-1211 Geneva, Switzerland
5. Geneva Neuroscience Center, CH-1211 Geneva, Switzerland
6. These authors contributed equally to this work.
good question took me a wile to find this, i hope it answers your questions... the answer is slightly yes, and you should ber able to put it down and walk away for a month or 2. thats what i have found.