title: Hooked on benzodiazepines: GABAA receptor subtypes and addiction.
abstract: 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.
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Tan
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
authors.forename: Christian
authors.initials: C
authors.lastname: Lüscher
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy; D016739:Behavior, Addictive; D001569:Benzodiazepines / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D018757:GABA Modulators / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D012201:Reward; D019966:Substance-Related Disorders / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D021122:Protein Subunits; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D004298:Dopamine