Voigt Jörg-Peter, Hörtnagl Heide, Rex André, van Hove Lil, Bader Michael, Fink Heidrun
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Brain Res. 2005 Jun 7;1046(1-2):145-56. doi: 10.1016/j.brainres.2005.03.048.
The transgenic rat TGR(ASrAOGEN)680, characterized by a transgene-producing antisense RNA against angiotensinogen in the brain, provides an opportunity to study the behavioral effects of angiotensin. While exposed to the elevated plus-maze (EPM) and the light/dark box, TGR(ASrAOGEN)680 rats showed more signs of anxiety compared to parental Sprague-Dawley (SD) rats. In the EPM, they made fewer entries into the open arms, spent less time there and more time on the closed arms. Head dips were reduced and U-turns were increased. In the light/dark box, the latency to the first re-entry into the light compartment was higher in TGR(ASrAOGEN)680. They displayed more SAP out from the dark and a reduced number of transitions between the two compartments. In the social interaction test, active social contacts were reduced, further suggesting an anxious phenotype. Although there was no transgenic effect on distance traveled in the open field, the more anxious TGR(ASrAOGEN)680 spent less time in the inner zone. Self-grooming was increased in TGR(ASrAOGEN)680 during exposure to the EPM and the open field, but was decreased in the social interaction test. In TGR(ASrAOGEN)680, tissue content of 5-HT and its metabolite 5-HIAA was lower in the hippocampus, frontal, and parietal cortex. HIAA and 5-HIAA/5-HT ratios were reduced in the hypothalamus, striatum, and septum. In the open field, the anxiogenic effect of the 5-HT2C/1B receptor agonist mCPP (0.5-1 mg/kg IP) was more pronounced in TGR(ASrAOGEN)680. The data suggest an anxious phenotype in rats with low brain angiotensinogen, possibly related to secondary dysfunctions of the brain serotonergic system.
转基因大鼠TGR(ASrAOGEN)680的特征是其转基因能在大脑中产生针对血管紧张素原的反义RNA，这为研究血管紧张素的行为效应提供了一个机会。在高架十字迷宫（EPM）和明暗箱实验中，与亲代斯普拉格-道利（SD）大鼠相比，TGR(ASrAOGEN)680大鼠表现出更多焦虑迹象。在EPM实验中，它们进入开放臂的次数更少，在开放臂停留的时间更短，而在封闭臂停留的时间更长。头部下探次数减少，U形转弯次数增加。在明暗箱实验中，TGR(ASrAOGEN)680大鼠首次重新进入亮区的潜伏期更长。它们从暗区出来的次数更多，在两个区域之间的转换次数减少。在社交互动测试中，主动社交接触减少，进一步表明其具有焦虑表型。尽管在旷场实验中，转基因对大鼠行进距离没有影响，但更焦虑的TGR(ASrAOGEN)680大鼠在内部区域停留的时间更短。在EPM和旷场实验中，TGR(ASrAOGEN)680大鼠的自我梳理行为增加，但在社交互动测试中则减少。在TGR(ASrAOGEN)680大鼠中，海马体、额叶和顶叶皮质中5-羟色胺（5-HT）及其代谢物5-羟吲哚乙酸（5-HIAA）的组织含量较低。下丘脑、纹状体和隔区中的5-HIAA和5-HIAA/5-HT比值降低。在旷场实验中，5-HT2C/1B受体激动剂mCPP（0.5-1毫克/千克腹腔注射）对TGR(ASrAOGEN)680大鼠的致焦虑作用更为明显。数据表明，脑内血管紧张素原水平低的大鼠具有焦虑表型，这可能与脑血清素能系统的继发性功能障碍有关。
