Role of dopamine D1 receptors in the activation of nucleus accumbens extracellular signal-regulated kinase (ERK) by cocaine-paired contextual cues.
Role of dopamine D1 receptors in the activation of nucleus accumbens extracellular signal-regulated kinase (ERK) by cocaine-paired contextual cues.
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DOI：
10.1038/npp.2010.174
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发表时间：
2011-01
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影响因子：
--
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暴露于药物配对的线索可能会引发成瘾者重新寻求药物。虽然线索诱导可卡因寻找的分子机制还不完全清楚，但已知蛋白激酶细胞外信号调节激酶（ERK）发挥重要作用。精神兴奋剂及其相关信号可以激活中脑核核心区（AcbC）中型多刺神经元中的ERK。这些中等多刺神经元可以根据它们的投射（腹侧苍白球和/或黑质）和它们的mRNA表达进行分类。本实验旨在确定哪组不同的AcbC投射神经元表达pERK，以响应可卡因配对的上下文线索。结合使用逆行标记Flurogold与pERK的免疫组织化学染色，显示AcbC pERK伴随可卡因配对的情况下发生在黑质和苍白球的预测。用原位杂交和免疫细胞化学相结合的方法进一步研究了可卡因配对刺激下表达pERK的神经元的基因表达特征，结果表明AcbC pERK+细胞对应于D1，而不是前脑啡肽原mRNA+细胞。此外，D1拮抗剂SCH 23390的AcbC内输注减弱了线索诱导的AcbC pERK表达。总的来说，这些结果表明，（i）D1表达的AcbC神经元证据长期可塑性相关的药物线索记忆，和（ii）本地多巴胺D1受体是必要的可卡因配对线索诱导的pERK在这些AcbC神经元的表达。
Exposure to drug-paired cues can trigger addicts to relapse into drug seeking. Although the molecular mechanisms underlying cue-elicited cocaine seeking are incompletely understood, the protein kinase extracellular signal–regulated kinase (ERK) is known to play an important role. Psychostimulants and their associated cues can activate ERK in medium spiny neurons of the nucleus accumbens core (AcbC). These medium spiny neurons can be classified according to their projections (to ventral pallidum and/or substantia nigra) and by their mRNA expression. The present experiments were designed to determine which distinct set of AcbC projection neurons expresses pERK in response to cocaine-paired contextual cues. Combined use of the retrograde label Flurogold with immunohistochemical staining of pERK was used to show that the AcbC pERK accompanying preference for cocaine-paired contexts occurs in both the accumbens-nigral and accumbens-pallidal projections. The gene expression characteristics of the neurons expressing pERK in response to cocaine-paired cues was further investigated using combined in situ hybridization and immunocytochemistry to show that AcbC pERK+ cells correspond to D1, but not preproenkephalin, mRNA+ cells. Furthermore, intra-AcbC infusion of the D1 antagonist SCH23390 attenuated cue-induced AcbC pERK expression. In aggregate, these results indicate that (i) the D1-expressing AcbC neurons evidence long-term plasticity related to drug-cue memories, and (ii) local dopamine D1 receptors are necessary for the expression of cocaine-paired cue-induced pERK in these AcbC neurons.
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影响因子：
2.7
作者：
Badiani, A;Oates, MM;Robinson, TE
通讯作者：
Robinson, TE
影响因子：
2.5
作者：
CURRAN, EJ;WATSON, SJ
通讯作者：
WATSON, SJ
影响因子：
2.9
作者：
CERVO, L;SAMANIN, R
通讯作者：
SAMANIN, R
影响因子：
56.9
作者：
GERFEN, CR;ENGBER, TM;SIBLEY, DR
通讯作者：
SIBLEY, DR
DOI：
10.1073/pnas.98.4.1976
发表时间：
2001-02-13
影响因子：
11.1
作者：
Ciccocioppo, R;Sanna, PP;Weiss, F
通讯作者：
Weiss, F