Braszko Jan J
Department of Clinical Pharmacology, Medical Academy of Bialystok, Ludwik Zamenhof Childrens Hospital, J. Waszyngtona St. 15 A, 15-274, Bialystok, Poland.
Behav Brain Res. 2002 Apr 1;131(1-2):79-86. doi: 10.1016/s0166-4328(01)00349-7.
In this study we attempted to determine behavioural, including cognitive, consequences of the brain AT(1) (losartan, 2 nmol), AT(2) (PD 123319, 1.5 nmol), and joint AT(1)/AT(2) angiotensin receptors blockade. Male Wistar rats (160-180 g) were injected into the left cerebral ventricle with the above doses of the blockers dissolved in 0.9% NaCl solution (vehicle) or with the vehicle alone. Five minutes later they received, to the right cerebral ventricle, 1 nmol of angiotensin II (Ang II) dissolved in vehicle or the vehicle alone. Ang II consistently increased rate of acquisition of conditioned avoidance response (CARs) and facilitated recall of the passive avoidance behaviour. In one out of the three series of experiments in open field Ang II stimulated rats locomotor activity. Losartan and PD 123319, both ineffective alone, given prior to Ang II abolished all the behavioural changes produced by the peptide except for the Ang II facilitation of CARs acquisition, which was unchanged by losartan. Interestingly, joint injection of losartan and PD 123319 significantly decreased the rate of CARs acquisition both in control and Ang II treated animals. In conclusion, the present data suggest significant though different involvement of both AT(1) and AT(2) angiotensin receptors in cognitive processes.
在本研究中，我们试图确定大脑中AT(1)（氯沙坦，2纳摩尔）、AT(2)（PD 123319，1.5纳摩尔）以及联合AT(1)/AT(2)血管紧张素受体阻断后的行为后果，包括认知后果。将体重160 - 180克的雄性Wistar大鼠的左脑室注射溶解于0.9%氯化钠溶液（赋形剂）中的上述剂量阻断剂，或仅注射赋形剂。五分钟后，给它们的右脑室注射溶解于赋形剂中的1纳摩尔血管紧张素II（Ang II）或仅注射赋形剂。Ang II持续增加条件性回避反应（CARs）的习得率，并促进被动回避行为的回忆。在旷场实验的三个系列中的一个系列里，Ang II刺激了大鼠的运动活动。氯沙坦和PD 123319单独使用均无效，在Ang II之前给予时，它们消除了该肽产生的所有行为变化，但Ang II对CARs习得的促进作用不受氯沙坦影响。有趣的是，氯沙坦和PD 123319联合注射显著降低了对照组和Ang II处理组动物的CARs习得率。总之，目前的数据表明AT(1)和AT(2)血管紧张素受体在认知过程中虽有不同但都有显著参与。
