Zhou L W, Zhang S P, Connell T A, Weiss B
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia.
J Pharmacol Exp Ther. 1993 Feb;264(2):824-30.
Behavioral and anatomical evidence supports an interaction between the dopaminergic and cholinergic systems in regulating certain behavioral conditions and motor functions. In this study, we utilized the cholinotoxin, acetylethylcholine mustard aziridinium ion (AF64A), to lesion the mouse corpus striatum in order to examine the role of cholinergic interneurons in striatum on cholinergic- and dopaminergic-mediated rotational behavior. Mice were unilaterally lesioned with AF64A and then challenged with a variety of dopaminergic and cholinergic agonists and antagonists. The results show that mice with AF64A-induced lesions rotate ipsilaterally to challenge doses of the dopamine agonists, apomorphine and pergolide, but rotate contralaterally to challenge injections of the cholinergic agonist, oxotremorine. The gamma aminobutyric acid (GABA) agonist, muscimol, and the M1 agonist, (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride failed to elicit rotational behavior. The D1 dopamine receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, inhibited rotations induced by apomorphine at concentrations 10-fold lower than those needed to block the effects of pergolide. However, the D2 dopamine receptor antagonist, sulpiride, blocked pergolide-induced rotations at concentrations about 4-fold lower than those needed to inhibit apomorphine-induced rotational behavior. Atropine blocked oxotremorine-induced contralateral rotations but enhanced apomorphine- and pergolide-induced ipsilateral rotations induced in AF64A-lesioned mice. Atropine was 10 times more effective in blocking oxotremorine-induced rotations than was the M3 antagonist, 4-diphenylacetoxy-N-methyl piperidine methiodide, and was 100 times more potent than the M2 and M1 antagonist, N,N'-bis[6-[[(2- methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride, or the M1 antagonist, pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)
行为学和解剖学证据支持多巴胺能系统与胆碱能系统在调节特定行为状态和运动功能方面存在相互作用。在本研究中，我们利用胆碱毒素乙酰乙基胆碱氮芥氮丙啶离子（AF64A）损伤小鼠纹状体，以研究纹状体胆碱能中间神经元在胆碱能和多巴胺能介导的旋转行为中的作用。小鼠单侧注射AF64A造成损伤，然后用多种多巴胺能和胆碱能激动剂及拮抗剂进行刺激。结果显示，AF64A诱导损伤的小鼠对多巴胺激动剂阿扑吗啡和培高利特的刺激剂量向同侧旋转，但对胆碱能激动剂氧化震颤素的注射刺激向对侧旋转。γ-氨基丁酸（GABA）激动剂蝇蕈醇和M1激动剂（4-羟基-2-丁炔基）-1-三甲基氯化铵氯代间氯卡巴腙未能引发旋转行为。D1多巴胺受体拮抗剂盐酸R（+）-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓在比阻断培高利特作用所需浓度低10倍的浓度下就能抑制阿扑吗啡诱导的旋转。然而，D2多巴胺受体拮抗剂舒必利在比抑制阿扑吗啡诱导的旋转行为所需浓度低约4倍时就能阻断培高利特诱导的旋转。阿托品阻断氧化震颤素诱导的对侧旋转，但增强AF64A损伤小鼠中阿扑吗啡和培高利特诱导的同侧旋转。阿托品阻断氧化震颤素诱导的旋转的效果比M3拮抗剂4-二苯乙酰氧基-N-甲基哌啶甲基碘化物强10倍，比M2和M1拮抗剂N,N'-双[6-[[（2-甲氧基苯基）甲基]氨基]己基]-1,8-辛二胺四盐酸盐或M1拮抗剂哌仑西平强100倍。（摘要截选至250词）
