Harro J, Kiivet R A, Lang A, Vasar E
Department of Pharmacology, Tartu University, Estonia U.S.S.R..
Behav Brain Res. 1990 Jun 18;39(1):63-71. doi: 10.1016/0166-4328(90)90121-t.
Rats with high and low exploratory activity in an elevated plus-maze model of anxiety were separated into subgroups termed 'non-anxious' and 'anxious' respectively according to the number of sectors the animals crossed and the total amount of time they spent in the open part of the plus-maze. The binding parameters of benzodiazepine and cholecystokinin octapeptide (CCK-8) receptors in frontal cortex and hippocampus of selected animals were studied and compared to an animal group representing the total mean scores and to home-cage controls. It was established that anxious rats had a significantly lower number of benzodiazepine receptors in frontal cortex as compared to non-anxious animals and in hippocampus as compared to home-cage controls. There was also a decreased number of CCK-8 receptors in hippocampus of anxious rats as compared to the non-anxious and control groups. Non-anxious animals had a significantly lower number of CCK-8 receptors in frontal cortex than anxious and control rats. Acute treatment of rats with anxiogenic benzodiazepine inverse agonist FG 7142 (10 and 20 mg/kg) did not influence benzodiazepine binding in brain regions under investigation but caused upregulation of CCK-8 receptor binding in frontal cortex. On the other hand, CCK-8 analogues caerulein and pentagastrin, administered in doses which inhibit exploratory activity in plus-maze (100 or 500 ng/kg respectively), decreased the number of benzodiazepine binding sites in rat frontal cortex if injected intraperitoneally but did not affect CCK-8 binding. The present findings indicate that benzodiazepine and CCK-8 receptor binding characteristics in brain undergo rapid and behaviourally specific changes during stressful events.
在高架十字迷宫焦虑模型中,根据大鼠穿越的扇区数量以及它们在十字迷宫开放部分所花费的总时间,将具有高探索活性和低探索活性的大鼠分别分为“非焦虑”和“焦虑”亚组。研究并比较了所选动物额叶皮质和海马体中苯二氮䓬和胆囊收缩素八肽(CCK - 8)受体的结合参数,与代表总平均分数的动物组以及笼养对照组进行比较。结果表明,与非焦虑动物相比,焦虑大鼠额叶皮质中的苯二氮䓬受体数量显著减少;与笼养对照组相比,海马体中的苯二氮䓬受体数量也显著减少。与非焦虑组和对照组相比,焦虑大鼠海马体中的CCK - 8受体数量也减少。非焦虑动物额叶皮质中的CCK - 8受体数量比焦虑大鼠和对照大鼠显著减少。用致焦虑的苯二氮䓬反向激动剂FG 7142(10和20 mg/kg)对大鼠进行急性处理,并未影响所研究脑区中的苯二氮䓬结合,但导致额叶皮质中CCK - 8受体结合上调。另一方面,以抑制十字迷宫探索活性的剂量(分别为100或500 ng/kg)腹腔注射CCK - 8类似物蛙皮素和五肽胃泌素,会减少大鼠额叶皮质中苯二氮䓬结合位点的数量,但不影响CCK - 8结合。目前的研究结果表明,在应激事件期间,大脑中苯二氮䓬和CCK - 8受体的结合特性会发生快速且具有行为特异性的变化。