Stress-Induced Potentiation of Cocaine Reward: A Role for CRFR1 and CREB
Stress-Induced Potentiation of Cocaine Reward: A Role for CRFR1 and CREB
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DOI：
10.1038/npp.2009.91
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发表时间：
2009-11-01
影响因子：
7.6
通讯作者：
Blendy, Julie A.
中科院分区：
文献类型：
--
作者：
Kreibich, Arati S.;Briand, Lisa;Blendy, Julie A.
临床和临床前研究都表明，应激可以加强药物使用；然而，这种相互作用的潜在机制尚不清楚。以前，我们已经证明，一次强迫游泳(FS)可以恢复对可卡因的条件性位置偏爱(CPP)，而cAMP反应元件结合蛋白(CREB)是这种反应所必需的。CREB可以被促肾上腺皮质激素释放因子(CRF)1型受体(CRFR1)结合激活，CRFR1介导对应激和药物滥用的神经内分泌和行为反应。本实验调查了先前应激引起的可卡因奖赏的变化是否由CREB和/或CRFR1介导。在条件作用前长期暴露于FS可增强野生型小鼠的可卡因CPP，但在CREB缺陷小鼠中这一作用被阻止。此外，在FS暴露前用CRFR1拮抗剂antalarmin预处理可阻断这种应激诱导的可卡因CPP的增强。此外，FS诱导的磷酸化CREB(PCREB)增加，特别是在外侧隔(LS)和伏隔核(NAC)，也可被安塔拉明阻断。综上所述，这些研究表明CREB和CRFR1的激活都是应激诱导的药物奖赏增强所必需的。神经精神药理学(2009年)34,2609-2617；DOI：10.1038/npp.2009.91；2009年8月12日在线发布
Both clinical and preclinical research have shown that stress can potentiate drug use; however, the underlying mechanisms of this interaction are unknown. Previously, we have shown that a single exposure to forced swim (FS) reinstates extinguished conditioned place preference (CPP) to cocaine and that cAMP response element binding protein (CREB) is necessary for this response. CREB can be activated by corticotropin releasing factor (CRF) receptor type 1 (CRFR1) binding, which mediates neuroendocrine and behavioral responses to stress as well as to drugs of abuse. The present experiments investigate whether changes in cocaine reward elicited by previous exposure to stress are mediated by CREB and/or CRFR1. Chronic exposure to FS in advance of conditioning enhances cocaine CPP in wild-type mice, but this is blocked in CREB-deficient mice. In addition, pretreatment with the CRFR1 antagonist, antalarmin, before FS exposure blocks this stress-induced enhancement of cocaine CPP. Furthermore, FS-induced increase in phosphorylated CREB (pCREB), specifically in the lateral septum (LS) and nucleus accumbens (NAc) is also blocked by antalarmin. Taken together, these studies suggest that both CREB and CRFR1 activation are necessary for stress-induced potentiation of drug reward. Neuropsychopharmacology (2009) 34, 2609-2617; doi:10.1038/npp.2009.91; published online 12 August 2009