Sienkiewicz-Jarosz H, Członkowska A I, Siemiatkowski M, Maciejak P, Szyndler J, Płaźnik A
Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
J Neural Transm (Vienna). 2000;107(12):1403-12. doi: 10.1007/s007020070004.
The aim of the study was to analyse in a well-established model of neophobia the effects of peripheral and central (ICV) administration of a prototypical and easily penetrating to the brain acetylcholinesterase inhibitor (AChE-I)--physostigmine, hemicholinium, a selective blocker of the high affinity choline uptake sites, as well as muscarinic and nicotinic receptor ligands. Thus, an attempt was made to address the question whether anxiolytic-like effects of AChE-I, reported in the clinic, are directly related to the anti-emotional action. The effects of peripherally and centrally administrated cholinergic ligands on novelty-induced decrease in exploratory behaviour were examined in rats. It was found that in a limited dose-range physostigmine and nicotine given peripherally or ICV selectively disinhibited rat exploration in the open field, whereas scopolamine stimulated animal motor activity and increased thigmotaxis. Locomotor effects of physostigmine and nicotine appeared at the higher doses and could be easily separated from their anti-neophobic action. The rat's exploratory behaviour tended to be attenuated by central administration of hemicholinium (a choline uptake blocker), and it was significantly inhibited by mecamylamine (a nicotinic receptor antagonist), and pirenzepine (a selective M1 receptor antagonist). Gallamine, a selective M2 receptor antagonist, did not influence on animal novelty-induced anxiety-related behaviour. It is concluded that AChE-I can selectively affect brain emotional processes evoked by neophobia-related stimuli. Probably both nicotinic and M1 cholinergic receptors mediate such an action of AChE-I.
本研究的目的是在一个成熟的新事物恐惧症模型中，分析外周和中枢（脑室内注射，ICV）给予一种典型且易于穿透血脑屏障的乙酰胆碱酯酶抑制剂（AChE-I）——毒扁豆碱、半胱氨酸（一种高亲和力胆碱摄取位点的选择性阻断剂）以及毒蕈碱和烟碱受体配体的作用。因此，试图解决临床上报道的AChE-I的抗焦虑样作用是否与抗情绪作用直接相关这一问题。在大鼠中检测了外周和中枢给予胆碱能配体对新事物诱导的探索行为减少的影响。结果发现，在有限的剂量范围内，外周或脑室内注射毒扁豆碱和尼古丁可选择性地解除大鼠在旷场中的探索抑制，而东莨菪碱则刺激动物的运动活动并增加趋触性。毒扁豆碱和尼古丁的运动效应出现在较高剂量时，且可轻易地与它们的抗新事物恐惧症作用区分开来。脑室内注射半胱氨酸（一种胆碱摄取阻断剂）会使大鼠的探索行为趋于减弱，而美加明（一种烟碱受体拮抗剂）和哌仑西平（一种选择性M1受体拮抗剂）则可显著抑制该行为。选择性M2受体拮抗剂加拉明对动物新事物诱导的焦虑相关行为没有影响。结论是，AChE-I可选择性地影响由新事物恐惧症相关刺激引发的大脑情绪过程。烟碱和M1胆碱能受体可能介导了AChE-I的这种作用。
