Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving.
Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving.
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DOI：
10.1016/j.biopsych.2009.02.009
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发表时间：
2009-07-15
影响因子：
10.6
通讯作者：
Shaham, Yavin
中科院分区：
文献类型：
--
作者：
Lu, Lin;Wang, Xi;Wu, Ping;Xu, Chunmei;Zhao, Mei;Morales, Marisela;Harvey, Brandon K.;Hoffer, Barry J.;Shaham, Yavin
关键词：
腹侧被盖区 (VTA) 脑源性神经营养因子 (BDNF) 有助于戒断后提示诱导的可卡因寻求时间依赖性增加（可卡因渴望的孵化）。在这里，我们研究了神经胶质细胞系衍生的神经营养因子（GDNF）在可卡因渴望孵化中的作用，因为与 BDNF 一样，GDNF 为中脑多巴胺神经元提供营养支持。我们首先训练大鼠自行静脉注射可卡因 10 天（每天 6 小时，可卡因注射与音调灯光提示配对）。然后，我们操纵 VTA GDNF 功能，并在戒断可卡因后的消退测试中评估提示诱导的可卡因寻求。戒断第 1 天，VTA 注射含有大鼠 GDNF cDNA（5 ×108 病毒基因组）的腺相关病毒 (AAV) 载体，可增加戒断第 11 天和第 31 天的提示诱导可卡因寻找；在 VTA 注射含有红色荧光蛋白 (RFP) 的 AAV 病毒载体后，未观察到这种效应。此外，在最后一次可卡因自我给药后立即注射 VTA（但不是大量黑质 (SN)）、GDNF（1.25 μg 或 12.5 μg/侧）会增加戒断第 3 天和第 10 天的提示诱导药物寻求；通过 VTA 注射 U0126 可以逆转这种效应，U0126 会抑制细胞外信号调节激酶 (ERK) 的活性。最后，在戒断第 1-14 天期间，通过微型泵（600 ng/侧/天）长期递送抗 GDNF 单克隆中和抗体来干扰 VTA GDNF 功能，可防止在戒断第 11 天和 31 天提示诱导的可卡因寻求的时间依赖性增加。我们的结果表明，在戒断可卡因自我给药的第一周内，中脑 VTA 神经元中的 GDNF 依赖性神经适应发挥着重要作用可卡因渴望的发展。
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. 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. 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 μg or 12.5 μg/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. Our results indicate that during the first weeks of withdrawal from cocaine self-administration, GDNF-dependent neuroad-aptations in midbrain VTA neurons play an important role in the development of incubation of cocaine craving.
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影响因子：
4.8
作者：
Chen, Yuan-Hao;Harvey, Brandon K.;Lupica, Carl R.
通讯作者：
Lupica, Carl R.
影响因子：
3.4
作者：
Airavaara, M;Planken, A;Ahtee, L
通讯作者：
Ahtee, L
影响因子：
120.7
作者：
BOZARTH, MA;WISE, RA
通讯作者：
WISE, RA
影响因子：
7.6
作者：
Freeman, Willard M.;Patel, Kruti M.;Vrana, Kent E.
通讯作者：
Vrana, Kent E.
DOI：
10.1073/pnas.0504438102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Ahmed, SH;Lutjens, R;Sanna, PP
通讯作者：
Sanna, PP