BACKGROUND & AIMS:
:Using the paradigm of habituation learning in the open field, we tested the effects of microinjections of the nonspecific acetylcholine-esterase inhibitor tacrine (0.1, 1.0, 10.0 micrograms), and the muscarinic receptor antagonist scopolamine (0.1, 1.0, 10.0 micrograms) into the core of the nucleus accumbens. When injected immediately after the first exposure to the open field (posttrial), tacrine dose-dependently enhanced habituation of rearing behavior during the test on the following day, indicating a facilitation of memory. In contrast, scopolamine impaired habituation of rearing behavior at the two lower doses, but not at the highest dose. When scopolamine or tacrine (10.0 micrograms) was injected with a delay of 5 h after the learning trial, both drugs impaired habituation of rearing on the following day. The effects on locomotor activity differed from those on rearing behavior. Here, habituation on Day 2 was observed only in those animals which had received posttrial injections of vehicle or 10 micrograms of tacrine on the day before, whereas in animals which had received the two lower doses of tacrine, locomotor activity on Day 2 was not significantly decreased. In animals with posttrial treatment of scopolamine, locomotor activity on Day 2 was even enhanced, especially with the lower doses. No such effects were observed when scopolamine or tacrine (10.0 micrograms each) was injected with a delay of 5 h after the learning trial. These results show that cholinergic manipulations aimed at the nucleus accumbens can have substantial effects in this posttrial memory paradigm, which depend on drug, dose, and time of injection, and the specific kind of behavioral measure analyzed. Among others, the findings are discussed with respect to the role of muscarinic and nicotinergic cholinergic mechanisms in the nucleus accumbens on cognitive functions. They may be relevant, for example, for understanding the psychopathology of Alzheimer's disease, since the nucleus accumbens is one of the sites where cholinergic neurons are lost in this neurodegenerative disease.
背景与目标:
:在野外使用习惯性学习范式,我们测试了将非特异性乙酰胆碱酯酶抑制剂他克林(0.1、1.0、10.0微克)和毒蕈碱受体拮抗剂东pol碱(0.1、1.0、10.0微克)微注射到小鼠体内的效果。伏伏核的核心。当他克林在第一次暴露于开阔视野(试验后)后立即注射时,其剂量依赖性地增强了第二天在测试过程中对养育行为的习惯,表明记忆得到了促进。相反,东pol碱在两个较低的剂量下会损害饲养行为的习惯,而在最高剂量下则不会。学习试验后5小时延迟注射东pol碱或他克林(10.0微克)时,两种药物均会损害第二天的饲养习惯。对运动活动的影响与对养育行为的影响不同。在此,仅在前一天接受了媒介物或10微克他克林注射后注射的那些动物中观察到了第2天的习惯,而在接受了两次较低剂量他克林的动物中,在第2天的运动能力没有显着变化减少了。在用东pol碱进行过事后治疗的动物中,第2天的运动能力甚至得到了增强,尤其是在使用较低剂量的情况下。在学习试验后延迟5小时注射东pol碱或他克林(各10.0微克)时,未观察到此类影响。这些结果表明,针对伏隔核的胆碱能操纵可在这种后记忆模型中产生实质性影响,这取决于药物,剂量和注射时间以及所分析的特定行为措施。除其他外,讨论的结果涉及毒蕈碱和烟碱能胆碱能机制在伏隔核中对认知功能的作用。例如,它们可能与了解阿尔茨海默氏病的心理病理有关,因为伏隔核是该神经退行性疾病中胆碱能神经元丢失的部位之一。