Pattern of c-fos mRNA induction in rat brain by acute morphine
Pattern of c-fos mRNA induction in rat brain by acute morphine
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DOI：
10.1139/cjpp-76-3-294
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发表时间：
1998-03-01
影响因子：
2.1
通讯作者：
Akil, H
中科院分区：
文献类型：
--
作者：
Gutstein, HB;Thome, JL;Akil, H
最初，阿片样物质信号被认为主要是抑制性的。然而，已经表明阿片类药物可以激活特定的信号通路并诱导脑中的立即早期基因（IEC）转录。然后，IEGs可以调节其他基因的转录，导致神经元功能响应细胞外刺激的变化。本研究的目的是确定大脑区域，表现出特定的诱导IEG c-fos，AP-1转录因子的一个组成部分，在急性吗啡，并将这种诱导与注射本身的压力效应。大鼠皮下注射10 mg/kg吗啡或等体积盐水。然后在注射后15、30或60分钟处死动物。吗啡对c-fos mRNA的特异性诱导见于背内侧尾壳核、丘脑室旁核、丘脑中央核和板内核、背侧中央灰质、上级丘、臂旁外侧核、下橄榄复合体和孤束尾侧核。这些发现代表了大鼠脑中c-fos诱导的第一个完整的解剖图，并表明急性吗啡给药改变了与阿片类药物已知功能特性相关的几个区域的基因表达。然而，显示c-fos诱导的区域并不都与阿片受体和阿片介导的效应经典相关。这些发现被认为是在阿片类药物对神经回路的影响以及吗啡对神经细胞的直接，受体介导的影响的背景下。
Initially, opioid signaling had been thought to be mainly inhibitory in nature. However, it has been shown that opioids can activate specific signaling pathways and induce immediate early gene (IEC) transcription in brain. IEGs can then regulate the transcription of other genes, leading to changes in neuronal function in response to extracellular stimuli. This study was designed to identify brain regions that demonstrate specific induction of the IEG c-fos, a component of the AP-1 transcription factor, in response to acute morphine, and to contrast this induction with the stressful effects of the injection itself. Rats received either 10 mg/kg morphine or an equivalent volume of saline injected subcutaneously. Animals were then sacrificed 15, 30, or 60 min after injection. Specific induction of c-fos mRNA by morphine was seen in dorsomedial caudate-putamen, paraventricular nucleus of the thalamus, central and intralaminar thalamic nuclei, dorsal central grey, superior colliculus, lateral parabrachial nucleus, inferior olivary complex, and caudal nucleus tractus solitarius. These findings represent the first complete anatomical mapping of c-fos induction in rat brain, and show that acute morphine administration alters gene expression in several areas related to known functional properties of opioids. However, regions showing c-fos induction are not all classically associated with opioid receptors and opioid-mediated effects. These findings are considered in the context of the effects of opioids on neural circuitry as well as direct, receptor-mediated effects of morphine on neural cells.