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Role of Ventral Tegmental Area Glial Cell Line–Derived Neurotrophic Factor in Incubation of Cocaine Craving
Lin Lu; Xi Wang; Ping Wu; Chunmei Xu; Mei Zhao; Marisela Morales; Brandon K. Harvey; Barry J. Hoffer; Yavin Shaham
First AuthorLin Lu
2009
Source PublicationBIOL PSYCHIATRY
Volume66Pages:66:137–145
Abstract

Background: Ventral tegmental area (VTA) brain-derived neurotrophic factor (BDNF) contributes to time-dependent increases in cueinduced 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: Wefirst trained rats to self-administer intravenous cocaine for 10 days (6 hours/d, cocaine injections were paired with a tone-light cue).Wethen 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_108 viral genomes) on withdrawal Day 1 increased cue-induced cocaine seeking on withdrawal days 11 and 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 _g or 12.5 _g/side) immediately after the last cocaine self-administration 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.

KeywordDrug self-administration ERK extinction glial cell line– derived neurotrophic factor growth factors reinstatement relapse ventral tegmental area
DOI10.1016/j.biopsych.2009.02.009
Language英语
Citation statistics
Cited Times:78[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/29144
Collection健康与遗传心理学研究室
Affiliation1.Peking University
2.National Institute on Drug Abuse, National Institute of Health
Recommended Citation
GB/T 7714
Lin Lu,Xi Wang,Ping Wu,等. Role of Ventral Tegmental Area Glial Cell Line–Derived Neurotrophic Factor in Incubation of Cocaine Craving[J]. BIOL PSYCHIATRY,2009,66:66:137–145.
APA Lin Lu.,Xi Wang.,Ping Wu.,Chunmei Xu.,Mei Zhao.,...&Yavin Shaham.(2009).Role of Ventral Tegmental Area Glial Cell Line–Derived Neurotrophic Factor in Incubation of Cocaine Craving.BIOL PSYCHIATRY,66,66:137–145.
MLA Lin Lu,et al."Role of Ventral Tegmental Area Glial Cell Line–Derived Neurotrophic Factor in Incubation of Cocaine Craving".BIOL PSYCHIATRY 66(2009):66:137–145.
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