Ushijima I, Kawano M, Kaneyuki H, Suetsugi M, Usami K, Hirano H, Mizuki Y, Yamada M
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Japan.
Pharmacol Biochem Behav. 1997 Sep;58(1):103-8. doi: 10.1016/s0091-3057(96)00478-9.
The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, were challenged by pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist. The effect of physostigmine and pilocarpine on haloperidol and SCH23390 cataleptic responses was also examined. Each of the challenging agents blocked one or more of the cataleptogenic agents, but only scopolamine blocked all four. Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous acetylcholine) on M2 receptors might be more potent than that on muscarinic M1 receptors. A further interesting observation was that the haloperidol-induced catalepsy was enhanced by physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two cholinergic agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological differences may be due largely to the different receptor subtypes that are involved in the mediation of catalepsy produced by each agent. Thus, dopamine receptors not only influence the cholinergic muscarinic receptors, but muscarinic M1 and M2 receptors also might mediate dopamine D1 and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2 receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independently of each other in influencing other system such as cholinergic neurons.
用多巴胺 D1 受体激动剂 SKF38393、多巴胺 D1/D2 受体激动剂（主要是 D2 受体）阿扑吗啡、毒蕈碱 M1 受体拮抗剂哌仑西平以及毒蕈碱 M1/M2 受体拮抗剂东莨菪碱对小鼠进行预处理，以对抗氟哌啶醇（一种多巴胺 D2 受体拮抗剂）、SCH23390（一种 D1 受体拮抗剂）、毒扁豆碱（一种胆碱酯酶抑制剂）和毛果芸香碱（一种毒蕈碱 M1 受体激动剂）的致僵作用。还研究了毒扁豆碱和毛果芸香碱对氟哌啶醇和 SCH23390 致僵反应的影响。每种挑战性药物都阻断了一种或多种致僵药物，但只有东莨菪碱阻断了所有四种。哌仑西平阻断了 SCH23390 和毛果芸香碱诱导的致僵反应，但未阻断氟哌啶醇和毒扁豆碱诱导的致僵反应。本研究结果表明，毒扁豆碱（内源性乙酰胆碱）对 M2 受体的作用可能比对毒蕈碱 M1 受体的作用更强。另一个有趣的观察结果是，氟哌啶醇诱导的僵住症通过毒扁豆碱预处理增强，但未通过毛果芸香碱预处理增强，而 SCH23390 诱导的僵住症在两种胆碱能激动剂作用下呈现相反的增强模式。我们得出结论，尽管这四种致僵药物通过多巴胺能 - 胆碱能系统起作用，但其药理差异可能主要归因于每种药物产生僵住症的介导过程中所涉及的不同受体亚型。因此，多巴胺受体不仅影响胆碱能毒蕈碱受体，而且毒蕈碱 M1 和 M2 受体也可能分别介导多巴胺 D1 和 D2 受体反应。结果表明，至少毒蕈碱 M1 受体与多巴胺能 D1 受体之间以及毒蕈碱 M2 和多巴胺能 D2 受体之间存在关联。多巴胺 D1 和 D2 受体在多巴胺能系统上可能以协同方式相互作用，但在影响其他系统（如胆碱能神经元）时彼此独立起作用。
