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Role of Ventral Tegmental Area Glial Cell Line-Derived Neurotrophic Factor in Incubation of Cocaine Craving
Lu, Lin1; Wang, Xi1; Wu, Ping1; Xu, Chunmei1; Zhao, Mei1; Morales, Marisela2; Harvey, Brandon K.2; Hoffer, Barry J.2; Shaham, Yavin2
关键词Drug self-administration ERK extinction glial cell line-derived neurotrophic factor growth factors reinstatement relapse ventral tegmental area
刊名BIOLOGICAL PSYCHIATRY
2009-07-15
DOI10.1016/j.biopsych.2009.02.009
66期:2页:137-145
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences ; Psychiatry
资助者National Institute on Drug Abuse (National Institutes of Health, U.S. Department of Health and Human Services) ; National Basic Research Program of China ; National High Technology Research and Development Program of China ; Natural Science Foundation of China ; National Institute on Drug Abuse (National Institutes of Health, U.S. Department of Health and Human Services) ; National Basic Research Program of China ; National High Technology Research and Development Program of China ; Natural Science Foundation of China
研究领域[WOS]Neurosciences & Neurology ; Psychiatry
关键词[WOS]ADENOASSOCIATED VIRAL VECTOR ; SIGNAL-TRANSDUCTION CASCADE ; MESOLIMBIC DOPAMINE SYSTEM ; MESSENGER-RNA EXPRESSION ; IN-VIVO ; PLACE PREFERENCE ; KNOCKOUT MICE ; SYNAPTIC PLASTICITY ; ALCOHOL-CONSUMPTION ; NUCLEUS-ACCUMBENS
英文摘要

Background: Ventral tegmental area (VTA) brain-derived neurotrophic factor (BDNF) contributes to time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Here, we studied the role of glial cell line-derived neurotrophic factor (GDNF) in incubation of cocaine craving because, like BDNF, GDNF provides trophic support to midbrain dopamine neurons.

Methods: We first trained rats to self-administer intravenous cocaine for 10 days (6 hours/d, cocaine injections were paired with a tone-light cue). We then manipulated VTA GDNF function and assessed cue-induced cocaine seeking in extinction tests after withdrawal from cocaine.

Results: VTA injections of an adeno-associated virus (AAV) vector containing rat GDNF cDNA (5 x 10(8) viral genomes) on withdrawal Day 1 increased cue-induced cocaine seeking on withdrawal days 1 land 31; this effect was not observed after VTA injections of an AAV viral vector containing red fluorescent protein (RFP). Additionally, VTA, but not substantial nigra (SN), GDNF injections (1.25 mu g or 12.5 mu g/side) immediately after the last cocaine self-ad ministration session increased cue-induced drug seeking on withdrawal days 3 and 10; this effect was reversed by VTA injections of U0126, which inhibits the activity of extracellular signal-regulated kinases (ERK). Finally, interfering with VTA GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies via minipumps (600 ng/side/d) during withdrawal Days 1-14 prevented the time-dependent increases in cue-induced cocaine seeking on withdrawal days 11 and 31.

Conclusions: Our results indicate that during the first weeks of withdrawal from cocaine self-administration, GDNF-dependent neuroadaptations in midbrain VTA neurons play an important role in the development of incubation of cocaine craving.

语种英语
所属项目编号2007CB512302 ; 2009CB522004 ; 2006AA02Z4D1 ; 30,670,713 ; 30,725,016
资助者National Institute on Drug Abuse (National Institutes of Health, U.S. Department of Health and Human Services) ; National Basic Research Program of China ; National High Technology Research and Development Program of China ; Natural Science Foundation of China ; National Institute on Drug Abuse (National Institutes of Health, U.S. Department of Health and Human Services) ; National Basic Research Program of China ; National High Technology Research and Development Program of China ; Natural Science Foundation of China
WOS记录号WOS:000267470400006
Citation statistics
Cited Times:76[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59412
Collection中国药物依赖性研究所
作者单位1.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
2.Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA
Recommended Citation
GB/T 7714
Lu, Lin,Wang, Xi,Wu, Ping,et al. Role of Ventral Tegmental Area Glial Cell Line-Derived Neurotrophic Factor in Incubation of Cocaine Craving[J]. BIOLOGICAL PSYCHIATRY,2009,66(2):137-145.
APA Lu, Lin.,Wang, Xi.,Wu, Ping.,Xu, Chunmei.,Zhao, Mei.,...&Shaham, Yavin.(2009).Role of Ventral Tegmental Area Glial Cell Line-Derived Neurotrophic Factor in Incubation of Cocaine Craving.BIOLOGICAL PSYCHIATRY,66(2),137-145.
MLA Lu, Lin,et al."Role of Ventral Tegmental Area Glial Cell Line-Derived Neurotrophic Factor in Incubation of Cocaine Craving".BIOLOGICAL PSYCHIATRY 66.2(2009):137-145.
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