Instituto de Neurociências and Comportamento-INeC, Campus USP, 14040-901 Ribeirão Preto, SP, Brazil.
Brain Res. 2009 Oct 19;1294:106-15. doi: 10.1016/j.brainres.2009.07.074. Epub 2009 Jul 30.
Serotonin (5-HT) plays a key role in the neural circuitry mediating unconditioned and conditioned fear responses related to panic and generalized anxiety disorders. The basolateral nucleus of the amygdala (BLA) and the dorsal periaqueductal gray (dPAG) appear to be mainly involved in these conditions. The aim of this study was to measure the extracellular level of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in the BLA and dPAG during unconditioned and conditioned fear states using in vivo microdialysis procedure. Thus, for the unconditioned fear test, animals were chemically stimulated in the dPAG with semicarbazide, an inhibitor of the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase. For the conditioned fear test, animals were subjected to a contextual conditioned fear paradigm using electrical footshock as the unconditioned stimulus. The results show that the 5-HT and 5-HIAA level in the BLA and dPAG did not change during unconditioned fear, whereas 5-HT concentration, but not 5-HIAA concentration, increased in these brain areas during conditioned fear. The present study showed that the 5-HT system was activated during conditioned fear, whereas it remained unchanged during unconditioned fear, supporting the hypothesis that 5-HT has distinct roles in conditioned and unconditioned fear (dual role of 5-HT in anxiety disorders).
血清素（5-HT）在介导与恐慌和广泛性焦虑障碍相关的无条件和条件恐惧反应的神经回路中发挥着关键作用。杏仁核基底外侧核（BLA）和背侧导水管周围灰质（dPAG）似乎主要涉及这些情况。本研究的目的是使用活体微透析程序测量 BLA 和 dPAG 中 5-HT 及其代谢物 5-羟吲哚乙酸（5-HIAA）在无条件和条件恐惧状态下的细胞外水平。因此，对于无条件恐惧测试，用半卡巴肼化学刺激 dPAG，半卡巴肼是γ-氨基丁酸合成酶谷氨酸脱羧酶的抑制剂。对于条件性恐惧测试，动物通过使用电脚刺激作为非条件刺激来进行情境条件性恐惧范式。结果表明，BLA 和 dPAG 中的 5-HT 和 5-HIAA 水平在无条件恐惧期间没有变化，而在这些脑区中，5-HT 浓度而非 5-HIAA 浓度在条件性恐惧期间增加。本研究表明，5-HT 系统在条件性恐惧期间被激活，而在无条件恐惧期间保持不变，这支持了 5-HT 在条件性和无条件恐惧中具有不同作用的假设（5-HT 在焦虑障碍中的双重作用）。
