Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning
文献类型：期刊论文
| 作者 | Liu ZQ1,2; Han J1,2; Jia LT2; Maillet JC2; Bai G3; Xu L4; Jia ZP5; Zheng QH2; Zhang WD6; Monette R6 |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2010 |
| 卷号 | 5期号:12页码:15634 |
| 通讯作者 | Xia.Zhang@rohcg.on.ca |
| 合作状况 | 其它 |
| 英文摘要 | Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity-or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction |
| 收录类别 | SCI |
| 资助信息 | This research was supported by a grant (MOP-62951) from Canadian Institutes of Health Research awarded to XZ who was a recipient of Independent Investigator Award from the National Alliance for Research on Schizophrenia and Depression (NARSAD) in the USA, and Cheung Kong Scholar (Chang Jiang Scholar) from the Chinese Education Ministry. |
| 语种 | 英语 |
| 公开日期 | 2011-01-29 |
| 源URL | [http://159.226.149.42:8088/handle/353002/6558]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.College of Life Sciences, Shaanxi Normal University, Xian, People’s Republic of China 2.Institute of Mental Health Research and Departments of Psychiatry and Cellular & Molecular Medicine, University of Ottawa, Ottawa, Canada 3.Department of Neural and Pain Sciences, Dental School, Program in Neuroscience, University of Maryland, Baltimore, Maryland, United States of America 4.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, People’s Republic of China 5.Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada 6.Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada 7.Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China |
| 推荐引用方式 GB/T 7714 | Liu ZQ,Han J,Jia LT,et al. Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning[J]. PLOS ONE,2010,5(12):15634. |
| APA | Liu ZQ.,Han J.,Jia LT.,Maillet JC.,Bai G.,...&Zhang X[*].(2010).Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning.PLOS ONE,5(12),15634. |
| MLA | Liu ZQ,et al."Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning".PLOS ONE 5.12(2010):15634. |
入库方式： OAI收割
来源：昆明动物研究所
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