School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, United Kingdom.
Pharmacol Biochem Behav. 2010 Oct;96(4):429-37. doi: 10.1016/j.pbb.2010.07.001. Epub 2010 Jul 16.
This study investigated risk assessment and anxiolytic/anxiogenic drug effects in "low brain angiotensinogen" transgenic rats (TGR) in comparison to wild-type Sprague-Dawley rats (SD) in the canopy test of anxiety-related behaviour. TGR showed a higher frequency of the risk assessment behaviour as indicated by performance of stretched attend posture (SAP) compared to SD. Diazepam (0.25mg/kg) reduced SAP in both strains, whereas FG-7142 had no significant effect. The 5-HT(1B/2C) agonist mCPP (0.5-2mg/kg) reduced SAP in both strains. Diazepam (0.25-1mg/kg) increased head dips and decreased the time spent under the canopy in SD rats. There were significant anxiogenic effects of both FG-7142 (3-6 mg/kg) and mCPP (0.5-2mg/kg) on these parameters for SD but not TGR. Diazepam (1mg/kg) increased the number of entries into the open zone in both strains. mCPP reduced this parameter in SD (2mg/kg) and TGR (0.5-2mg/kg). FG-7142 had a similar effect in SD (3-6 mg/kg) and TGR (6 mg/kg). This study showed a significant transgenic effect on SAP. The increased number of SAP seen in TGR could be reduced with diazepam. Although both FG-7142 and mCPP are generally anxiogenic, no significant effects of FG-7142 on SAP were observed and mCPP even reduced SAP.
本研究在焦虑相关行为的顶棚试验中,比较了“低脑血管紧张素原”转基因大鼠(TGR)和野生型 Sprague-Dawley 大鼠(SD)的风险评估和抗焦虑/致焦虑药物效应。与 SD 相比,TGR 表现出更高的风险评估行为频率,表现为伸展姿势(SAP)。地西泮(0.25mg/kg)降低了两种品系的 SAP,而 FG-7142 没有显著影响。5-HT(1B/2C)激动剂 mCPP(0.5-2mg/kg)降低了两种品系的 SAP。地西泮(0.25-1mg/kg)增加了 SD 大鼠的头部倾斜和减少了在顶棚下的时间。FG-7142(3-6mg/kg)和 mCPP(0.5-2mg/kg)对这些参数都有明显的致焦虑作用,但对 TGR 没有影响。地西泮(1mg/kg)增加了两种品系进入开放区域的次数。mCPP 降低了 SD(2mg/kg)和 TGR(0.5-2mg/kg)的这一参数。FG-7142 对 SD(3-6mg/kg)和 TGR(6mg/kg)有类似的作用。本研究显示了 SAP 上的显著转基因效应。TGR 中看到的 SAP 数量增加可以用地西泮减少。尽管 FG-7142 和 mCPP 通常都是致焦虑的,但 FG-7142 对 SAP 没有显著影响,而 mCPP 甚至降低了 SAP。