A heuristic model of alcohol dependence.
A heuristic model of alcohol dependence.
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DOI：
10.1371/journal.pone.0092221
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Voit EO
中科院分区：
文献类型：
--
作者：
Qi Z;Tretter F;Voit EO
物质依赖是一个严重的健康问题。可悲的是，它的神经生物学机制仍然不清楚，这种缺乏真正理解的情况反映在治疗选择不足上。有假设认为，酒精的作用是由于神经兴奋性氨基酸和神经抑制性氨基酸之间的失衡。然而，谷氨酸和GABA与其他神经递质相互作用，形成一个复杂的网络，其功能逃避直觉，需要用生物医学系统分析的方法进行系统研究。我们提出了一个神经递质的启发式模型，该模型结合了生化水平上的神经化学相互作用矩阵和描述生理和行为水平上神经递质对之间的平衡的移动体。我们在这两个水平上研究了酒精对整合神经递质系统的影响。模型模拟结果与临床和实验观察结果基本一致。该模型表明，治疗酒精戒断症状的药物安定有效地减少了神经递质之间的失衡。此外，乙酰胆碱信号被认为是治疗酒精戒断相关症状的新靶点。在多个层面上整合临床症状的有效手段仍然很少，而且很难建立。我们提出了一个系统神经递质功能的启发式模型，该模型允许评估遗传、生化和药物扰动。该模型可以作为一种工具来代表临床和生物学观察，并探索与酒精依赖及其治疗相关的各种情景。它也非常适合用于教育目的。
Substance dependence poses a critical health problem. Sadly, its neurobiological mechanisms are still unclear, and this lack of real understanding is reflected in insufficient treatment options. It has been hypothesized that alcohol effects are due to an imbalance between neuroexcitatory and neuroinhibitory amino acids. However, glutamate and GABA interact with other neurotransmitters, which form a complicated network whose functioning evades intuition and should be investigated systemically with methods of biomedical systems analysis. We present a heuristic model of neurotransmitters that combines a neurochemical interaction matrix at the biochemical level with a mobile describing the balances between pairs of neurotransmitters at the physiological and behavioral level. We investigate the effects of alcohol on the integrated neurotransmitter systems at both levels. The model simulation results are consistent with clinical and experimental observations. The model demonstrates that the drug diazepam for symptoms of alcohol withdrawal effectively reduces the imbalances between neurotransmitters. Moreover, the acetylcholine signal is suggested as a novel target for treatment of symptoms associated with alcohol withdrawal. Efficient means of integrating clinical symptoms across multiple levels are still scarce and difficult to establish. We present a heuristic model of systemic neurotransmitter functionality that permits the assessment of genetic, biochemical, and pharmacological perturbations. The model can serve as a tool to represent clinical and biological observations and explore various scenarios associated with alcohol dependence and its treatments. It also is very well suited for educational purposes.
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影响因子：
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