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Facilitation of dopamine-dependent long-term potentiation in the medial prefrontal cortex of male rats follows the behavioral effects of stress.
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-09-20 , DOI: 10.1002/jnr.24732
Jacopo Lamanna 1, 2 , Francesco Isotti 1, 2 , Mattia Ferro 1, 3 , Gabriella Racchetti 1, 4 , Lavinia Anchora 1 , Daniele Rucco 1 , Antonio Malgaroli 1, 2
Affiliation  

The effect of stress on animal behavior and brain activity has been attracting growing attention in the last decades. Stress dramatically affects several aspects of animal behavior, including motivation and cognitive functioning, and has been used to model human pathologies such as post‐traumatic stress disorder. A key question is whether stress alters the plastic potential of synaptic circuits. In this work, we evaluated if stress affects dopamine (DA)‐dependent synaptic plasticity in the medial prefrontal cortex (mPFC). On male adolescent rats, we characterized anxiety‐ and depressive‐like behaviors using behavioral testing before and after exposure to a mild stress (elevated platform, EP). After the behavioral protocols, we investigated DA‐dependent long‐term potentiation (DA‐LTP) and depression (DA‐LTD) on acute slices of mPFC and evaluated the activation of DA‐producing brain regions by western and dot blot analysis. We show that exposure to the EP stress enhances DA‐LTP and that desipramine (DMI) treatment abolishes this effect. We also found that DA‐LTD is not affected by EP stress unless when this is followed by DMI treatment. In addition, EP stress reduces anxiety, an effect abolished by both DMI and ketamine, while motivation is promoted by previous exposure to EP stress independently of pharmacological treatments. Finally, this form of stress reduces the expression of the early gene cFOS in the ventral tegmental area. These findings support the idea that mild stressors can promote synaptic plasticity in PFC through a dopaminergic mechanism, an effect that might increase the sensitivity of mPFC to subsequent stressful experiences.

中文翻译:

雄性大鼠内侧前额叶皮层中多巴胺依赖性长期增强的促进遵循压力的行为影响。

在过去的几十年里,压力对动物行为和大脑活动的影响越来越受到关注。压力会显着影响动物行为的多个方面,包括动机和认知功能,并已被用于模拟人类病理,如创伤后应激障碍。一个关键问题是压力是否会改变突触回路的可塑性。在这项工作中,我们评估了压力是否会影响内侧前额叶皮层 (mPFC) 中依赖于多巴胺 (DA) 的突触可塑性。在雄性青春期大鼠身上,我们在暴露于轻度压力(高平台,EP)之前和之后使用行为测试来表征焦虑和抑郁样行为。在行为协议之后,我们研究了 mPFC 急性切片上的 DA 依赖性长时程增强 (DA-LTP) 和抑制 (DA-LTD),并通过蛋白质印迹分析和斑点印迹分析评估了产生 DA 的大脑区域的激活。我们表明,暴露于 EP 压力会增强 DA-LTP,而地昔帕明 (DMI) 治疗消除了这种影响。我们还发现 DA‐LTD 不受 EP 应力的影响,除非随后进行 DMI 处理。此外,EP 压力可减少焦虑,DMI 和氯胺酮都消除了这种影响,而先前暴露于 EP 压力而与药物治疗无关,从而促进了动机。最后,这种形式的压力降低了腹侧被盖区早期基因 cFOS 的表达。这些发现支持了以下观点,即轻度压力源可以通过多巴胺能机制促进 PFC 中的突触可塑性,
更新日期:2020-09-20
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