Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and University of Copenhagen, Denmark; Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Neuropharmacology. 2018 Jul 1;136(Pt C):411-420. doi: 10.1016/j.neuropharm.2017.09.011. Epub 2017 Sep 11.
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level. These studies revealed important functions of muscarinic receptors modulating neuronal activity and neurotransmitter release in many brain regions, shaping neuronal plasticity, and affecting functions ranging from motor and sensory function to cognitive processes. As gene targeting technology evolves including the use of conditional, cell type specific strains, knockout mice are likely to continue to provide valuable insights into brain physiology and pathophysiology, and advance the development of new medications for a range of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and addictions, as well as non-opioid analgesics. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.
由于五种毒蕈碱乙酰胆碱受体亚型在许多中枢神经系统组织中分布重叠，并且对于特定亚型具有高度选择性的配体长期难以捉摸，因此很难确定每个受体的生理功能。在中枢神经系统中，通过基因工程敲除小鼠（一种或多种毒蕈碱乙酰胆碱受体亚型已失活），有助于确定毒蕈碱受体的功能，包括神经元、回路和行为水平。这些研究揭示了毒蕈碱受体在许多脑区调节神经元活动和神经递质释放、塑造神经元可塑性以及影响从运动和感觉功能到认知过程等功能的重要作用。随着基因靶向技术的发展，包括使用条件性、细胞类型特异性品系，敲除小鼠可能会继续为大脑生理学和病理生理学提供有价值的见解，并推进一系列疾病（如阿尔茨海默病、帕金森病、精神分裂症和成瘾）以及非阿片类镇痛药的新药物的开发。本文是题为“毒蕈碱受体的神经药理学”特刊的一部分。
