精神刺激药物苯(并)二氮在临床和娱乐方面被广泛使用，虽然它们短期被认为是安全和有效的，但对某些人来说却容易上瘾。迄今所研究的所有成瘾药物都有增加中脑边缘区域中多巴胺水平、触发腹侧被盖区中适应性突触可塑性的作用。
一项新的研究表明，苯(并)二氮（通过与GABAA受体结合发挥作用）也能通过对附近中间神经元中含alpha-1的GABAA受体的正调节增加腹侧被盖区中多巴胺神经元的激发。这种作用反过来又会触发多巴胺神经元中由药物引发的突触可塑性。该研究数据还表明，不激发alpha-1受体的亚单元选择性苯(并)二氮可能不会让人上瘾。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 463, 769-774 (11 February 2010) | doi:10.1038/nature08758
Neural bases for addictive properties of benzodiazepines
Kelly R. Tan1, Matthew Brown1,6, Gwena?l 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.
7 Correspondence to: Christian Lüscher1,4,5 Correspondence and requests for materials should be addressed to C.L.
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.
