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Hooked on benzodiazepines: GABAA receptor subtypes and addiction

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Titel: Hooked on benzodiazepines: GABAA receptor subtypes and addiction
Autoren: Tan, Kelly, Rudolph, Uwe, Luescher, Christian
Quelle: ISSN: 0166-2236 ; Trends in neurosciences, vol. 34, no. 4 (2011) p. 188-197.
Publikationsjahr: 2011
Bestand: Université de Genève: Archive ouverte UNIGE
Schlagwörter: info:eu-repo/classification/ddc/616.8, Animals, Anxiety Disorders/drug therapy, Behavior, Addictive, Benzodiazepines/adverse effects/metabolism/therapeutic use, Dopamine/metabolism, GABA Modulators/adverse effects/metabolism/therapeutic use, Humans, Neurons/metabolism, Protein Subunits/metabolism, Receptors, GABA-A/metabolism, Reward, Substance-Related Disorders/physiopathology, Ventral Tegmental Area/metabolism
Beschreibung: 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.
Publikationsart: article in journal/newspaper
Sprache: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/21353710; unige:26928
Verfügbarkeit: https://archive-ouverte.unige.ch/unige:26928
Rights: info:eu-repo/semantics/restrictedAccess
Dokumentencode: edsbas.C47A97D4
Datenbank: BASE
Beschreibung
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.