Hawkins C A, Greenfield S A
University Department of Pharmacology, Oxford, UK.
Pharmacol Biochem Behav. 1996 Sep;55(1):67-80. doi: 10.1016/0091-3057(96)00050-0.
It has been postulated for many years that acetylcholinesterase (AChE) may play a nonclassical role in the substantia nigra, unrelated to its ability to hydrolyse acetylcholine. In this study the behavioural effects of unilateral infusion of AChE and a cholinergic agonist, carbachol, were compared. Carbachol induced ipsiversive circling over a very short time scale (minutes), whereas AChE induced contraversive circling, but over a longer time course-10 days. Both agents showed selectivity of response within the substantia nigra: acetylcholinesterase was only effective when infused into the most rostral region of the substantia nigra and its effects were limited to the pars compacta. In contrast, carbachol had effects in both the pars compacta and reticulata, with a graded sensitivity to carbachol in the rostral/caudal plane; infusions into rostral regions induced high rates of circling compared to more caudal areas, suggesting that the cholinergic input to the substantia nigra is not homogenous, but greater in rostral regions. This disparity between the effects of carbachol and AChE would, therefore, suggest that AChE is not exerting its long-term behavioural actions via a cholinergic mechanism, both in terms of time course of the response and the areas within the substantia nigra sensitive to these agents.
多年来一直有人推测，乙酰胆碱酯酶（AChE）可能在黑质中发挥非经典作用，这与其水解乙酰胆碱的能力无关。在本研究中，比较了单侧注入AChE和胆碱能激动剂卡巴胆碱的行为效应。卡巴胆碱在很短的时间尺度（数分钟）内诱导同侧旋转，而AChE诱导对侧旋转，但时间进程较长，为10天。两种药物在黑质内均表现出反应选择性：乙酰胆碱酯酶仅在注入黑质最前端区域时有效，且其作用仅限于致密部。相比之下，卡巴胆碱在致密部和网状部均有作用，在前后平面上对卡巴胆碱具有分级敏感性；与更靠尾侧的区域相比，注入前端区域会诱导更高的旋转速率，这表明黑质的胆碱能输入并非均匀一致，而是在前端区域更强。因此，卡巴胆碱和AChE作用之间的这种差异表明，无论是从反应的时间进程还是从黑质内对这些药物敏感的区域来看，AChE都不是通过胆碱能机制发挥其长期行为作用的。
