Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation,ACS Chemical Neuroscience

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Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2017-08-18 00:00:00 , DOI: 10.1021/acschemneuro.7b00156
Fuencisla Pilar-Cuéllar _{1,

2,

3} , Rebeca Vidal _{4,

5,

6} , Álvaro Díaz _{1,

2,

3} , Emilio Garro-Martínez _{1,

2,

3} , Raquel Linge _{1,

2,

3} , Elena Castro _{1,

2,

3} , Robert Haberzettl ₇ , Heidrun Fink ₇ , Bettina Bert ₇ , Jan Brosda ₇ , Beatriz Romero _{1,

2,

3} , Benedicto Crespo-Facorro _{1,

8} , Ángel Pazos _{1,

2,

3}

Affiliation

Postsynaptic 5-HT_1A receptors (5-HT_1AR) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT_1ARs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT_1ARs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT_1AR overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT_1AR activation might predispose to a high anxious phenotype and an impaired stress coping behavior.

中文翻译：

5-HT _1A R过表达小鼠中增强的应激反应：改变的HPA功能和海马长期增强。

突触后5-HT _1A受体（5-HT _1A R）在焦虑和压力中起着重要作用，尽管它们的作用仍存在争议。先前的研究报告说，虽然尚未解决应激条件的影响，但过表达突触后5-HT _1A Rs的小鼠基础焦虑没有变化。在这项研究中，我们使用这种动物模型来评估5-HT _1A Rs在预先暴露于急性应激源后的焦虑反应中的作用。在基础条件下，5-HT _1AR过表达的动物表现出较高的皮质酮水平和较低的盐皮质激素/糖皮质激素受体比率。在预先暴露于单个应激源后，它们表现出高度的焦虑样反应，与皮质酮水平的平缓增加和前额叶皮层中较高的c-Fos活化有关。而且，这些小鼠在暴露于应激后还表现出缺乏下调海马长时程增强的作用。因此，较高的突触后5-HT _1A R激活可能会导致高焦虑表型和应激应对行为受损。

更新日期：2017-08-19

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