Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal.

Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal.
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DOI:
10.1111/j.1460-9568.2010.07148.x
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发表时间:
2010-03
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Shinnick-Gallagher P
Shinnick-Gallagher P
中科院分区:
其他
文献类型:
--
作者:
Krishnan B;Centeno M;Pollandt S;Fu Y;Genzer K;Liu J;Gallagher JP;Shinnick-Gallagher P

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杏仁核中的促肾上腺皮质激素释放因子(CRF)参与应激反应。此外,包括杏仁核在内的大脑奖赏系统中的多巴胺能神经传递在可卡因成瘾的病理过程中发挥着重要作用。我们的研究分析了CRF诱导的突触可塑性、其药理学敏感性,以及在反复戒断可卡因两周后,CRF与基底外侧(BLA)至中央杏仁核(LcCeA)外侧被膜(LcCeA)通路中多巴胺(DA)系统的相互作用。生理上相关的CRF浓度(25 NM)诱导的长时程增强(LTP)在可卡因戒断后增强。在生理盐水处理的大鼠,CRF诱导的LTP是通过N-甲基-D-天冬氨酸受体、L型电压门控钙通道和CRF1受体介导的。然而,在可卡因戒断的动物中,CRF1和CRF2受体的激活被发现可以提高LTP。这种增强CRF在可卡因戒断后诱导的LTP的作用是通过内源性激活D1样和D2样受体来实现的。此外,戒断后D1R的表达显著增加,而D2R、D3R、D4R和D5R的表达无明显变化。研究还发现CRF1而不是CRF2蛋白的表达增加,这表明这些蛋白的水平升高有助于CRF在可卡因戒断过程中诱导的LTP的增强。总之,CRF与杏仁核DA系统的相互作用可能代表了将应激与可卡因诱导的神经元可塑性联系起来的基本神经化学和细胞机制。
Corticotropin releasing factor (CRF) in the amygdala is involved in stress responses. Moreover, dopaminergic neurotransmission in the brain reward system including the amygdala plays a significant role in the pathology of cocaine addiction. Our study analyzed CRF-induced synaptic plasticity, its pharmacological sensitivity, and interactions with the dopamine (DA) system in the basolateral (BLA) to lateral capsula central amygdala (lcCeA) pathway after a two week withdrawal from repeated cocaine administration. A physiologically relevant CRF concentration (25 nM) induced long-term potentiation (LTP) that was enhanced after cocaine withdrawal. In saline-treated rats, CRF-induced LTP was mediated through N-methyl-D-aspartate (NMDA) receptors, L-type voltage gated calcium channels (L-VGCCs), and CRF1 receptors. However, in cocaine-withdrawn animals, activation of CRF1 and CRF2 receptors was found to enhance LTP. This enhanced CRF-induced LTP after cocaine withdrawal was mediated through endogenous activation of both D1-like and D2-like receptors. Furthermore, expression of the D1 receptor (D1R) but not the D2R, D3R, D4R or D5R was significantly increased after cocaine withdrawal. It was also found that CRF1 but not CRF2 protein expression was increased suggesting that elevated levels of these proteins contributed to the enhancement of CRF-induced LTP during cocaine withdrawal. In summary, CRF interactions with the DA system in the amygdala may represent a fundamental neurochemical and cellular mechanism linking stress to cocaine-induced neuronal plasticity.
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