精神刺激藥物苯(并)二氮在臨床和娛樂(lè)方面被廣泛使用,，雖然它們短期被認(rèn)為是安全和有效的,，但對(duì)某些人來(lái)說(shuō)卻容易上癮。迄今所研究的所有成癮藥物都有增加中腦邊緣區(qū)域中多巴胺水平,、觸發(fā)腹側(cè)被蓋區(qū)中適應(yīng)性突觸可塑性的作用,。
一項(xiàng)新的研究表明，苯(并)二氮（通過(guò)與GABAA受體結(jié)合發(fā)揮作用）也能通過(guò)對(duì)附近中間神經(jīng)元中含alpha-1的GABAA受體的正調(diào)節(jié)增加腹側(cè)被蓋區(qū)中多巴胺神經(jīng)元的激發(fā),。這種作用反過(guò)來(lái)又會(huì)觸發(fā)多巴胺神經(jīng)元中由藥物引發(fā)的突觸可塑性,。該研究數(shù)據(jù)還表明，不激發(fā)alpha-1受體的亞單元選擇性苯(并)二氮可能不會(huì)讓人上癮,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
