Sienkiewicz-Jarosz H, Maciejak Piotr, Krzaścik Paweł, Członkowska Agnieszka I, Szyndler Janusz, Bidziński Andrzej, Kostowski Wojciech, Płaźnik Adam
1st Department of Neurology, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
Pharmacol Biochem Behav. 2003 May;75(2):491-6. doi: 10.1016/s0091-3057(03)00141-2.
The effects of intracerebroventricular and intraseptal (the medial septum) administration of a prototypical acetylcholinesterase inhibitor (AChE-I), physostigmine, and a classic benzodiazepine midazolam on rat behavior in the open field test of neophobia and in the conditioned fear test (freezing reaction) were examined in rats. In the open field test of neophobia midazolam and physostigmine increased at a limited dose range, rat exploratory activity, after intracerebroventricular injection. Physostigmine produced in addition the hyperlocomotory effect. Following intraseptal injections, only physostigmine selectively prolonged the time spent by animals in the central sector of the open field. In the model of a conditioned fear, both midazolam and physostigmine inhibited rat freezing reaction to the aversively conditioned context after intracerebroventricular, but not after intraseptal, pretrial drug administration. The presented data support the notion about the selective anxiolytic-like effects of some AChE-Is. It appears, therefore, that the calming and sedative effects of AChE-Is observed in patients with Alzheimer's disease may be directly related to their anxiolytic action, independent of an improvement in cognitive functions, which in turn may decrease disorientation-induced distress and anxiety.
研究了向大鼠脑室内和中隔（内侧隔）注射典型的乙酰胆碱酯酶抑制剂（AChE-I）毒扁豆碱和经典苯二氮䓬类药物咪达唑仑，对大鼠在新物恐惧旷场试验和条件性恐惧试验（僵住反应）中的行为的影响。在新物恐惧旷场试验中，咪达唑仑和毒扁豆碱在有限剂量范围内，经脑室内注射后可增加大鼠的探索活动。此外，毒扁豆碱还产生了运动亢进效应。经中隔注射后，只有毒扁豆碱选择性地延长了动物在旷场中央区域停留的时间。在条件性恐惧模型中，经脑室内而非中隔内注射药物预处理后，咪达唑仑和毒扁豆碱均能抑制大鼠对厌恶条件化情境的僵住反应。所呈现的数据支持了某些AChE-I具有选择性抗焦虑样作用的观点。因此，在阿尔茨海默病患者中观察到的AChE-I的镇静和安定作用，可能与其抗焦虑作用直接相关，而与认知功能的改善无关，认知功能的改善反过来可能会减少定向障碍引起的痛苦和焦虑。
