Georgiev V
Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Acad. G. Bonchev, Sofia.
Pol J Pharmacol Pharm. 1990 Nov-Dec;42(6):553-62.
The behavioural effects of angiotensin II (AT II) were studied using the following paradigms: seizures (threshold and intensity) in mice; active avoidance (shuttle-box) in rats; passive avoidance (step through) in rats; exploratory activity (open field) in rats; apomorphine stereotypy in rats. The involvement of DA- and GABA-ergic transmitter mechanisms in the effects of AT II was also studied. It was found that AT II increased the seizure threshold and decreased the seizure intensity, the effects being potentiated by DA- and GABA-ergic agonists and prevented by DA- and GABA-ergic antagonists. AT II effect on seizure threshold was stronger when AT II was applied after withdrawal of repeatedly injected DA-ergic antagonist pimozide. AT II improved retention in active and passive avoidance tasks. This effect was potentiated by DA- and GABA-ergic agonists. Postrial saralasin and haloperidol abolished the retention-facilitating effect of AT II. Bicuculline and picrotoxin abolished the influence of GABAA-ergic agonists on the memory effect of AT II. AT II changed exploratory behaviour in a nonlinear dose-effect manner. The stimulant effects of AT II were antagonized by saralasin, increased by apomorphine and nomifensine and decreased by haloperidol and alpha-methyl-para-tyrosine (alpha MpT). AT II enhanced apomorphine stereotypy; the effect was decreased by saralasin and alpha MpT, and abolished by haloperidol. These results suggest that the behavioural effects of AT II are mediated by interactions with brain AT II receptors. DA and GABA receptors modulate in some way the AT II activity.
使用以下范式研究了血管紧张素II（AT II）的行为效应：小鼠的癫痫发作（阈值和强度）；大鼠的主动回避（穿梭箱）；大鼠的被动回避（一步通过）；大鼠的探索活动（旷场）；大鼠的阿扑吗啡刻板行为。还研究了多巴胺能和γ-氨基丁酸能递质机制在AT II效应中的作用。结果发现，AT II提高了癫痫发作阈值并降低了发作强度，多巴胺能和γ-氨基丁酸能激动剂可增强这些效应，而多巴胺能和γ-氨基丁酸能拮抗剂则可阻止这些效应。当在反复注射多巴胺能拮抗剂匹莫齐特后停药时应用AT II，其对癫痫发作阈值的影响更强。AT II改善了主动和被动回避任务中的记忆保持。多巴胺能和γ-氨基丁酸能激动剂可增强这种效应。试验后注射沙拉新和氟哌啶醇可消除AT II的记忆促进作用。荷包牡丹碱和印防己毒素可消除GABAA能激动剂对AT II记忆效应的影响。AT II以非线性剂量效应方式改变探索行为。沙拉新可拮抗AT II的兴奋作用，阿扑吗啡和诺米芬辛可增强其作用，氟哌啶醇和α-甲基-对酪氨酸（α-MpT）可降低其作用。AT II增强了阿扑吗啡刻板行为；沙拉新和α-MpT可降低这种效应，氟哌啶醇可消除这种效应。这些结果表明，AT II的行为效应是通过与脑AT II受体的相互作用介导的。多巴胺和γ-氨基丁酸受体以某种方式调节AT II的活性。
