Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking.
Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking.
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DOI：
10.1016/j.neuropharm.2013.07.001
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发表时间：
2013-12
影响因子：
4.7
通讯作者：
Addy NA
中科院分区：
文献类型：
--
作者：
Solecki W;Wickham RJ;Behrens S;Wang J;Zwerling B;Mason GF;Addy NA
暴露于与药物相关的线索会引起寻求药物的行为，被认为是复吸的主要原因。提示引起腹侧被盖区（VTA）多巴胺（DA）神经元的爆发性放电和中脑核（NAc）的阶段性DA释放。胆碱能和多巴胺能输入到腹侧被盖区的门控相DA活动。然而，VTA胆碱能和多巴胺能受体在调节阶段性多巴胺释放和线索诱导的药物寻求可卡因经验的科目的作用是未知的。在雄性Sprague-Dawley大鼠中，我们发现VTA失活强烈抑制，而VTA刺激促进，可卡因寻求行为在早期戒断。阻断NAc核心中的阶段性激活的D1受体也强烈抑制线索诱导的可卡因寻求-这表明阶段性DA活性在VTA至NAc核心电路中的重要作用。接下来，我们研究了VTA乙酰胆碱受体（AChRs）和N-甲基-D-天冬氨酸受体（NMDARs）在调节NAc核心阶段DA释放和线索诱导的可卡因寻找中的作用。在可卡因初治受试者中，VTA输注烟碱乙酰胆碱受体（AChR）拮抗剂美加明、毒蕈碱AChR拮抗剂东莨菪碱或NMDAR拮抗剂AP-5，导致NAc核心中阶段性DA释放的强烈衰减。在早期可卡因戒断过程中，VTA输注AP-5对NAc阶段性DA释放和线索诱导的可卡因寻求的影响有限，而VTA输注美加明或东莨菪碱强烈抑制阶段性DA释放和可卡因寻求。结果表明，VTA AChRs，但不是NMDARs，强烈调节线索诱导的可卡因寻求和阶段性DA释放早期可卡因戒断过程中。
Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Cues evoke burst firing of ventral tegmental area (VTA) dopamine (DA) neurons and phasic DA release in the nucleus accumbens (NAc). Cholinergic and glutamatergic input to the VTA is suggested to gate phasic DA activity. However, the role of VTA cholinergic and glutamatergic receptors in regulating phasic dopamine release and cue-induced drug-seeking in cocaine experienced subjects is not known. In male Sprague-Dawley rats, we found that VTA inactivation strongly inhibited, while VTA stimulation promoted, cocaine-seeking behavior during early withdrawal. Blockade of phasic activated D1 receptors in the NAc core also strongly inhibited cue-induced cocaine-seeking - suggesting an important role of phasic DA activity in the VTA to NAc core circuit. Next, we examined the role of VTA acetylcholine receptors (AChRs) and N-methyl-D-aspartate receptors (NMDARs) in regulating both NAc core phasic DA release and cue-induced cocaine-seeking. In cocaine naïve subjects, VTA infusion of the nicotinic acetylcholine receptor (AChR) antagonist mecamylamine, the muscarinic AChR antagonist scopolamine, or the NMDAR antagonist AP-5, led to robust attenuation of phasic DA release in the NAc core. During early cocaine withdrawal, VTA infusion of AP-5 had limited effects on NAc phasic DA release and cue-induced cocaine-seeking while VTA infusion of mecamylamine or scopolamine robustly inhibited both phasic DA release and cocaine-seeking. The results demonstrate that VTA AChRs, but not NMDARs, strongly regulate cue-induced cocaine-seeking and phasic DA release during early cocaine withdrawal.
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影响因子：
16.2
作者：
Lüscher C;Malenka RC
通讯作者：
Malenka RC
影响因子：
3.4
作者：
Mahler, Stephen V.;Smith, Rachel J.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary
影响因子：
2.3
作者：
OVERTON, P;CLARK, D
通讯作者：
CLARK, D
影响因子：
1.7
作者：
Lester, Deranda B.;Miller, Anthony D.;Blaha, Charles D.
通讯作者：
Blaha, Charles D.
DOI：
10.1523/jneurosci.2246-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
通讯作者：
de Lecea L