Distinct patterns of ΔFosB induction in brain by drugs of abuse
Distinct patterns of ΔFosB induction in brain by drugs of abuse
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DOI：
10.1002/syn.20500
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发表时间：
2008-05-01
期刊：
影响因子：
2.3
通讯作者：
Nestler, E. J.
中科院分区：
文献类型：
--
作者：
Perrotti, L. I.;Weaver, R. R.;Nestler, E. J.
转录因子δ FosB在大脑对慢性刺激的反应中积累并持续存在。长期暴露于药物滥用后的这种积累在纹状体区域（包括背纹状体（尾状核/壳核）和伏隔核）中表现得最为显著。在本研究中，我们使用免疫组织化学技术以更高的解剖学精度定义了慢性药物治疗后整个啮齿动物大脑中Delta FosB的诱导。我们还将先前涉及可卡因、吗啡和尼古丁的研究扩展到另外两种滥用药物：乙醇和德尔塔(9)-四氢大麻酚（德尔塔(9)-四氢大麻酚，大麻中的有效成分）。我们在这里表明，慢性而非急性地服用可卡因、吗啡、乙醇和δ(9)-四氢大麻酚这四种滥用药物中的每一种，都能强烈地诱导伏隔核中的δ FosB，尽管不同药物在伏隔核的核区和壳区表现出明显的不同模式。两种药物对背纹状体FosB的诱导程度也不同。此外，四种药物均可诱导前额叶皮层的δ FosB，其中可卡因和乙醇的作用最大，并且所有药物均可在杏仁核中产生小程度的δ FosB。此外，所有药物都能诱导海马中的δ FosB，除乙醇外，这种诱导主要发生在齿状体中。在对特定药物治疗的反应中，在大脑的其他区域可以看到较低水平的δ FosB诱导。这些发现进一步证明，在伏隔核中诱导三角FosB是几乎所有滥用药物的共同作用，并且除了伏隔核之外，每种药物在大脑中以特定区域的方式诱导三角FosB。
The transcription factor Delta FosB accumulates and persists in brain in response to chronic stimulation. This accumulation after chronic exposure to drugs of abuse has been demonstrated previously by Western blot most dramatically in striatal regions, including dorsal striatum (caudate/putamen) and nucleus accumbens. In the present study, we used immunohistochemistry to define with greater anatomical precision the induction of Delta FosB throughout the rodent brain after chronic drug treatment. We also extended previous research involving cocaine, morphine, and nicotine to two additional drugs of abuse, ethanol and Delta(9)-tetrahydrocannabinol (Delta(9)-THC, the active ingredient in marijuana). We show here that chronic, but not acute, administration of each of four drugs of abuse, cocaine, morphine, ethanol, and Delta(9)-THC, robustly induces Delta FosB in nucleus accumbens, although different patterns in the core vs. shell subregions of this nucleus were apparent for the different drugs. The drugs also differed in their degree of Delta FosB induction in dorsal striatum. In addition, all four drugs induced Delta FosB in prefrontal cortex, with the greatest effects observed with cocaine and ethanol, and all of the drugs induced Delta FosB to a small extent in amygdala. Furthermore, all drugs induced Delta FosB in the hippocampus, and, with the exception of ethanol, most of this induction was seen in the dentate. Lower levels of Delta FosB induction were seen in other brain areas in response to a particular drug treatment. These findings provide further evidence that induction of Delta FosB in nucleus accumbens is a common action of virtually all drugs of abuse and that, beyond nucleus accumbens, each drug induces Delta FosB in a region-specific manner in brain.