Fear is an adaptive component of the acute "stress" response to potentially-dangerous (external and internal) stimuli which threaten to perturb homeostasis. However, when disproportional in intensity, chronic and/or irreversible, or not associated with any genuine risk, it may be symptomatic of a debilitating anxious state: for example, social phobia, panic attacks or generalized anxiety disorder. In view of the importance of guaranteeing an appropriate emotional response to aversive events, it is not surprising that a diversity of mechanisms are involved in the induction and inhibition of anxious states. Apart from conventional neurotransmitters, such as monoamines, gamma-amino-butyric acid (GABA) and glutamate, many other modulators have been implicated, including: adenosine, cannabinoids, numerous neuropeptides, hormones, neurotrophins, cytokines and several cellular mediators. Accordingly, though benzodiazepines (which reinforce transmission at GABA(A) receptors), serotonin (5-HT)(1A) receptor agonists and 5-HT reuptake inhibitors are currently the principle drugs employed in the management of anxiety disorders, there is considerable scope for the development of alternative therapies. In addition to cellular, anatomical and neurochemical strategies, behavioral models are indispensable for the characterization of anxious states and their modulation. Amongst diverse paradigms, conflict procedures--in which subjects experience opposing impulses of desire and fear--are of especial conceptual and therapeutic pertinence. For example, in the Vogel Conflict Test (VCT), the ability of drugs to release punishment-suppressed drinking behavior is evaluated. In reviewing the neurobiology of anxious states, the present article focuses in particular upon: the multifarious and complex roles of individual modulators, often as a function of the specific receptor type and neuronal substrate involved in their actions; novel targets for the management of anxiety disorders; the influence of neurotransmitters and other agents upon performance in the VCT; data acquired from complementary pharmacological and genetic strategies and, finally, several open questions likely to orientate future experimental- and clinical-research. In view of the recent proliferation of mechanisms implicated in the pathogenesis, modulation and, potentially, treatment of anxiety disorders, this is an opportune moment to survey their functional and pathophysiological significance, and to assess their influence upon performance in the VCT and other models of potential anxiolytic properties.

中文翻译：

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神经生物学和焦虑状态的控制。

恐惧是对潜在危险（外部和内部）刺激的急性“压力”反应的一种适应性成分，这种刺激可能会扰乱稳态。但是，如果强度，长期和/或不可逆或与任何真正的风险不成比例，则可能表现出令人衰弱的焦虑状态：例如，社交恐惧症，惊恐发作或广泛性焦虑症。考虑到确保对厌恶事件做出适当的情绪反应的重要性，毫不奇怪的是，多种机制参与了焦虑状态的诱导和抑制。除了传统的神经递质（例如单胺，γ-氨基丁酸（GABA）和谷氨酸）外，还涉及许多其他调节剂，包括：腺苷，大麻素，许多神经肽，激素，神经营养蛋白，细胞因子和几种细胞介体。因此，尽管苯二氮卓类药物（可增强GABA（A）受体的传递），5-羟色胺（5-HT）（1A）受体激动剂和5-HT再摄取抑制剂目前是治疗焦虑症的主要药物，但仍有相当大的范围用于开发替代疗法。除了细胞，解剖和神经化学策略外，行为模型对于表征焦虑状态及其调节也是必不可少的。在各种范式中，冲突程序（使受试者经历相反的欲望和恐惧冲动）具有特殊的概念和治疗针对性。例如，在Vogel冲突测试（VCT）中，评估了药物释放受惩罚抑制的饮酒行为的能力。在回顾焦虑状态的神经生物学时，本文特别着重于：各个调节剂的多种多样且复杂的作用，通常是其作用所涉及的特定受体类型和神经元底物的功能；治疗焦虑症的新目标；神经递质和其他药物对VCT性能的影响；从互补的药理和遗传策略中获得的数据，以及最后可能会影响未来实验和临床研究的几个悬而未决的问题。鉴于最近与发病机制，调节以及潜在的焦虑症治疗有关的机制激增，这是一个调查其功能和病理生理意义的时机，