Faculty of Psychology and Neuroscience, EURON, Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands.
Neurosci Biobehav Rev. 2010 Jul;34(8):1307-50. doi: 10.1016/j.neubiorev.2010.04.001. Epub 2010 Apr 14.
Scopolamine is used as a standard/reference drug for inducing cognitive deficits in healthy humans and animals. Effects are often interpreted in terms of a role of acetylcholine in mnemonic and/or attentional processes. In this paper an overview is given of the effects of scopolamine on animal behavior. Examination of the dose-response curve of systemically administered scopolamine indicates that sensory discrimination and attention are most sensitive to disruption. When higher doses (>0.03mg/kg) are used, deficits in other cognitive and non-cognitive functions (e.g., learning and memory, locomotor activity) are reported. Several behavioral processes (taste aversion, anxiety, short-term memory, attention) are found to be affected after intracerebral injections of scopolamine. It is concluded that effects on learning and memory performance which are observed after higher doses of scopolamine are mediated by (1) primary effects on attention and sensory/stimulus discrimination, (2) non-specific effects on behavior (e.g., locomotor activity, anxiety), and (3) peripheral side-effects (e.g., pupil dilation, salivation). Finally, the validity of scopolamine as a pharmacological model for cognitive impairment is discussed. The use of muscarinic M1 antagonists is suggested as a more selective and effective way of inducing cholinergic-induced cognitive deficits.
莨菪碱被用作诱导健康人类和动物认知缺陷的标准/参考药物。其作用通常被解释为乙酰胆碱在记忆和/或注意力过程中的作用。本文概述了莨菪碱对动物行为的影响。检查系统给予的莨菪碱的剂量-反应曲线表明，感觉辨别和注意力最容易受到干扰。当使用更高剂量（>0.03mg/kg）时，报告了其他认知和非认知功能（例如，学习和记忆，运动活动）的缺陷。发现脑内注射莨菪碱后，几种行为过程（味觉厌恶，焦虑，短期记忆，注意力）受到影响。结论是，在更高剂量的莨菪碱后观察到的学习和记忆性能的影响是由（1）对注意力和感觉/刺激辨别有直接作用，（2）对行为有非特异性作用（例如，运动活动，焦虑），和（3）外周副作用（例如，瞳孔扩张，唾液分泌）介导的。最后，讨论了莨菪碱作为认知障碍的药理学模型的有效性。建议使用毒蕈碱 M1 拮抗剂作为诱导胆碱能引起的认知缺陷的更具选择性和有效的方法。
