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成瘾研究中的系统观点。

The systems view in addiction research.

作者信息

Gebicke-Haerter Peter J, Tretter Felix

机构信息

Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Germany.

出版信息

Addict Biol. 2008 Sep;13(3-4):449-54. doi: 10.1111/j.1369-1600.2008.00137.x.

Abstract

The wealth of information accessible on the molecular level after completion of sequencing of the human and other genomes and in conjunction with new high-throughput technologies like microarrays has paved the way for research on whole systems rather than on single components. Here we describe exemplarily the construction of a rather complex molecular network involved in alcohol addiction by using information from DNA-microarray studies in alcohol-dependent animals. In this network, haemoglobin downregulation in different parts of the brain reward system plays a central role in affecting synaptic plasticity, circadian rhythmicity and opioid receptors. Furthermore, we discuss the dynamic aspect of biological systems with respect to repeated and intermittent drug intake. This aspect can best be captured by the allostatic model on the molecular level. Using a molecular oscillator model where levels of oscillations are changed by repetitive drug administration, changes in set point adjustment are described that underlay allostatic shifts in drug reinforcement processes.

摘要

在人类和其他基因组测序完成后,结合微阵列等新的高通量技术,分子水平上可获取的丰富信息为全系统而非单个组件的研究铺平了道路。在此,我们通过使用来自酒精依赖动物DNA微阵列研究的信息,示例性地描述了一个涉及酒精成瘾的相当复杂的分子网络的构建。在这个网络中,大脑奖赏系统不同部位的血红蛋白下调在影响突触可塑性、昼夜节律和阿片受体方面起着核心作用。此外,我们讨论了生物系统关于反复和间歇性药物摄入的动态方面。这一方面在分子水平上可以通过适应性负荷模型得到最好的体现。使用一个分子振荡器模型,其中振荡水平通过重复给药而改变,描述了设定点调整的变化,这些变化是药物强化过程中适应性负荷变化的基础。

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