Hooked on benzodiazepines: GABAA receptor subtypes and addiction

被引:220
|
作者
Tan, Kelly R. [1 ]
Rudolph, Uwe [2 ,3 ]
Luescher, Christian [1 ,4 ]
机构
[1] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland
[2] Harvard Univ, Sch Med, McLean Hosp, Lab Genet Neuropharmacol, Belmont, MA 02478 USA
[3] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA
[4] Univ Hosp Geneva, Neurol Clin, Dept Clin Neurosci, CH-1211 Geneva, Switzerland
基金
瑞士国家科学基金会;
关键词
VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE SYSTEM; AMINOBUTYRIC ACID(A) RECEPTORS; EVOKED SYNAPTIC PLASTICITY; CEREBELLAR GRANULE CELLS; LONG-TERM POTENTIATION; IN-VIVO MICRODIALYSIS; NUCLEUS-ACCUMBENS; BINDING-SITE; A RECEPTORS;
D O I
10.1016/j.tins.2011.01.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:188 / 197
页数:10
相关论文
共 50 条
  • [31] Hooked on hype: Addiction and responsibility
    Morse, SJ
    LAW AND PHILOSOPHY, 2000, 19 (01) : 3 - 49
  • [32] GABAA receptor subtypes as targets for neuropsychiatric drug development
    Korpi, ER
    Sinkkonen, ST
    PHARMACOLOGY & THERAPEUTICS, 2006, 109 (1-2) : 12 - 32
  • [33] Addiction to Benzodiazepines
    Carl Salzman
    Psychiatric Quarterly, 1998, 69 : 251 - 261
  • [34] BENZODIAZEPINES AND ADDICTION
    JUERGENS, SM
    PSYCHIATRIC CLINICS OF NORTH AMERICA, 1993, 16 (01) : 75 - 86
  • [35] GABAA/Bz receptor subtypes as targets for selective drugs
    Da Settimo, F.
    Taliani, S.
    Trincavelli, M. L.
    Montali, M.
    Martini, C.
    CURRENT MEDICINAL CHEMISTRY, 2007, 14 (25) : 2680 - 2701
  • [36] Getting hooked: rationality and addiction
    Levine, HG
    ADDICTION, 2000, 95 (03) : 449 - 452
  • [37] Addiction to benzodiazepines
    Salzman, C
    PSYCHIATRIC QUARTERLY, 1998, 69 (04) : 251 - 261
  • [38] Hooked on Hype: Addiction and Responsibility
    Stephen J. Morse
    Law and Philosophy, 2000, 19 (1) : 3 - 49
  • [39] An intersubunit electrostatic interaction in the GABAA receptor facilitates its responses to benzodiazepines
    Pflanz, Natasha C.
    Daszkowski, Anna W.
    Cornelison, Garrett L.
    Trudell, James R.
    Mihic, S. John
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (21) : 8264 - 8274
  • [40] The role of the α2 GABAA receptor subtype in mediating the rewarding properties of benzodiazepines
    Morris, HV
    Dawson, GR
    Reynolds, DS
    Stephens, DN
    BEHAVIOURAL PHARMACOLOGY, 2005, 16 : S82 - S83