Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats.

Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats.
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DOI:
10.3389/fncir.2016.00108
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发表时间:
2016
影响因子:
3.5
通讯作者:
Dagnino-Subiabre A
Dagnino-Subiabre A
中科院分区:
医学3区
文献类型:
--
作者:
Pérez-Valenzuela C;Gárate-Pérez MF;Sotomayor-Zárate R;Delano PH;Dagnino-Subiabre A

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慢性应激损害大鼠的听觉注意力,单胺类物质调节初级听觉皮质(A1)的神经传递,A1是调节听觉注意力的大脑区域。在此背景下,我们假设A1中的去甲肾上腺素(NE)水平与慢性应激大鼠的听觉注意表现相关。这项研究的第一个目标是评估慢性应激是否影响A1中的单胺水平。对雄性SD大鼠进行慢性应激(束缚应激),采用高效液相色谱-电化学检测法测定大鼠脑内单胺类物质水平。慢性应激大鼠A1区去甲肾上腺素水平低于对照组,而慢性应激不影响5-羟色胺(5-HT)和多巴胺(DA)水平。第二个目的是确定瑞波西汀(去甲肾上腺素再摄取的选择性抑制剂)对A1区听觉注意和去甲肾上腺素水平的影响。训练大鼠在两种选择任务(2-ACT)中辨别两种不同频率的音调,这是一种研究大鼠听觉注意的行为范式。训练后的动物在2-ACT中达到≥80%的正确率,被随机分配到对照组和应激试验组。为了分析慢性应激对大鼠听觉任务的影响,两组大鼠在慢性应激期前1天和后1天分别进行了50次2-ACT测试。差异分数(DS)是通过从慢性应激方案之前减去正确试验的次数来确定的。一个意想不到的结果是,服用安慰剂的对照组大鼠和服用安慰剂的慢性应激大鼠在注意任务中的表现相似,这表明反复注射安慰剂会给对照组动物带来压力,并使它们的听觉注意力恶化。在这一点上,接受瑞波西汀治疗的慢性应激大鼠的听觉注意力和A1区去甲肾上腺素水平高于服用安慰剂的大鼠。这些结果表明,去甲肾上腺素在应激大鼠辨别音调的A1和注意中起关键作用。
Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle-treated animals. These results indicate that NE has a key role in A1 and attention of stressed rats during tone discrimination.
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