抑郁大鼠扔水里拒绝游泳？

美国 ATS 公司的专利产品 Saporin 靶向毒素又获得了新的研究成果：

A2 noradrenergic neurons regulate forced swim test immobility.
Hyungwoo Nama, Ilan A. Kerman. Physiol Behav 165:339-349, 2016.

作者在文章中使用了 Anti-DBH-SAP (Cat. #IT-03)，对非抑郁 WIS 大鼠的 A2 去甲肾上腺素神经元进行靶向破坏，结果 WIS 大鼠像广泛应用的抑郁模型 WKY 大鼠一样，也在强迫游泳实验中拒绝运动！

如果您有意向在您的实验中使用靶向毒素 Saporin，欢迎垂询！

技术支持 QQ：2853711237

摘要翻译

Wistar-Kyoto(WKY) 大鼠是广泛应用的动物抑郁模型，其特点是去甲肾上腺素的信号传导失调。我们之前已经证实，大鼠在强迫游泳测试（forced swim test）中显示出独特的行为，与基因型相关的 Wistar 大鼠相比，WKY 大鼠初次强迫游泳试验中很少运动，再次试验时通过更少运动表现出较大的类学习反应。当前的研究旨在研究改变脑干去甲肾上腺素细胞的活性是否会促进这种行为模式。我们选择 WKY 和 Wistar 大鼠进行 5 分钟的强迫游泳或者标准的两天强迫游泳试验 (即第一天强制游泳 15 分钟，第二天强制游泳 5 分钟)。然后我们对他们大脑染色，用于 FOS 或络氨酸羟化酶双免疫组化检测活化的脑干去肾上腺素细胞组群的电位差。与 Wistars 大鼠的一天和两天强制游泳的试验进行对比，我们在 WKY 大鼠中发现一个相对超活性的蓝斑。相反，在这两天的强制游泳试验中， WKY 的 A2 去甲肾上腺素细胞群体中 FOS 水平降低，表明他们活性降低。随后，我们使用抗β-多巴胺氢化酶偶联的皂草素有选择的损伤 A2 神经元，并继续观察。结果表明，在两天的强制游泳试验中 Wistar 大鼠稳定性增加。这些数据表明，A2 去甲肾上腺素细胞组群调节 FST 行为，并且它的超活性可能对 WKY 大鼠这种独特的行为具有促进作用。

Abstract

The Wistar-Kyoto (WKY) rat is a widely used animal model of depression, which is characterized by dysregulation of noradrenergic signaling. We previously demonstrated that WKY rats show a unique behavioral profile on the forced swim test (FST), characterized by high levels of immobility upon initial exposure and a greater learning-like response by further increasing immobility upon re-exposure than the genetically related Wistar rats. In the current study we aimed to determine whether altered activation of brainstem noradrenergic cell groups contributes to this behavioral profile. We exposed WKY and Wistar rats, to either 5 min of forced swim or to the standard two-day FST (i.e. 15 min forced swim on Day 1, followed by 5 min on Day 2). We then stained their brains for FOS/tyrosine hydroxylase double-immunocytochemistry to determine potential differences in the activation of the brainstem noradrenergic cell groups. We detected a relative hyperactivation in the locus coeruleus of WKY rats when compared to Wistars in response to both one- and two-day forced swim. In contrast, within the A2 noradrenergic cell group, WKY rats exhibited diminished levels of FOS across both days of the FST, suggesting their lesser activation. We followed up these observations by selectively lesioning the A2 neurons, using anti-dopamine-β-hydroxylase-conjugated saporin, in Wistar rats, which resulted in increased FST immobility on both days of the test. Together these data indicate that the A2 noradrenergic cell group regulates FST behavior, and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats.

编辑： weicf    来源：丁香园