Kruk-Słomka Marta, Michalak Agnieszka, Budzyńska Barbara, Biała Grażyna
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland.
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland.
Pharmacol Rep. 2014 Aug;66(4):638-46. doi: 10.1016/j.pharep.2014.02.002. Epub 2014 Mar 2.
The aim of the present study was to evaluate the involvement of the cholinergic receptors ligands in the memory-related responses in mice, using the novel object recognition (NOR) test.
The NOR test is based on natural, exploratory abilities of animals exposed to a new environment. In the first session, two copies of the same object were presented. In the next sessions (30min and 24h after), one of the familiar object and a new object were presented.
The mice injected with nicotine (0.035 and 0.175mg/kg, free base, sc) before the first session spent more time exploring the new object than the familiar one at the second and third session, indicating that nicotine improved cognition. In turn, the mice injected with scopolamine (0.3 and 1mg/kg, ip) before the first session spent less time exploring the new object than the familiar one at the second and third trial, indicating that scopolamine impaired the memory performance. Additionally, the acute injection of drugs used in smoking cessation in humans: mecamylamine (0.5 and 1mg/kg) and bupropion (5 and 10mg/kg), prior to injections of nicotine (0.035mg/kg) or scopolamine (1mg/kg), significantly prevented nicotine-induced memory improvement or scopolamine-induced memory impairment, at the second and third session.
The results of our studies unveiling neuronal mechanisms for cholinergic system of memory processes, via both nicotinic and muscarinic cholinergic receptors, will be useful for development of more effective pharmacotherapies for memory impairment-like treatment of human disorders in which cholinergic pathways have been implicated.
本研究的目的是使用新颖物体识别(NOR)试验评估胆碱能受体配体在小鼠记忆相关反应中的作用。
NOR试验基于动物在新环境中的自然探索能力。在第一阶段,呈现两个相同物体的复制品。在接下来的阶段(30分钟和24小时后),呈现一个熟悉的物体和一个新物体。
在第一阶段前注射尼古丁(0.035和0.175mg/kg,游离碱,皮下注射)的小鼠在第二和第三阶段花费更多时间探索新物体而非熟悉物体,表明尼古丁改善了认知。相反,在第一阶段前注射东莨菪碱(0.3和1mg/kg,腹腔注射)的小鼠在第二和第三次试验中花费更少时间探索新物体而非熟悉物体,表明东莨菪碱损害了记忆表现。此外,在注射尼古丁(0.035mg/kg)或东莨菪碱(1mg/kg)之前,急性注射人类戒烟所用药物:美加明(0.5和1mg/kg)和安非他酮(5和10mg/kg),在第二和第三阶段显著预防了尼古丁诱导的记忆改善或东莨菪碱诱导的记忆损害。
我们的研究结果揭示了通过烟碱型和毒蕈碱型胆碱能受体的记忆过程胆碱能系统的神经元机制,这将有助于开发更有效的药物疗法来治疗类似记忆损害的人类疾病,其中胆碱能通路已被牵连。