Ikarashi Y, Takahashi A, Ishimaru H, Arai T, Maruyama Y
Department of Neuropsychopharmacology (Tsumura), Gunma University, School of Medicine, Japan.
Neurochem Int. 1997 Feb;30(2):191-7. doi: 10.1016/s0197-0186(96)00024-1.
The effect of dopamine (DA) D2 receptor on extracellular choline (Ch) and acetylcholine (ACh) levels in rat caudate-putamen (striatum) was investigated by means of microdialysis. The systemic, intraperitoneal (i.p.), injection of (+/-)-2-(N-phenylethyl-N-propyl) amino-5-hydroxytetralin (N-434), a specific DA D2 receptor agonist decreased striatal ACh release in a dose-dependent manner and the i.p. injection of sulpiride, a specific DA D2 receptor antagonist, increased the ACh release in a dose-dependent manner. In contrast, extracellular Ch levels were increased by the agonist and decreased by the antagonist. An increased Ch uptake was observed in sulpiride-treated rats and a decreased Ch uptake was observed in N-434-treated rats. The effects of the D2 agonist on extracellular Ch, ACh and Ch uptake were completely antagonized by the D2 antagonist. These results suggest clearly an inhibition of ACh release by D2 receptor activation, contrasting with previous findings on DA-ACh interaction. The inverse relationship between extracellular Ch and ACh reflects a change in the Ch uptake owing to a change in cholinergic neuron activity via the D2 receptor mechanisms.
采用微透析技术研究了多巴胺（DA）D2受体对大鼠尾状核-壳核（纹状体）细胞外胆碱（Ch）和乙酰胆碱（ACh）水平的影响。系统性腹腔注射特异性DA D2受体激动剂（±）-2-（N-苯乙基-N-丙基）氨基-5-羟基四氢萘（N-434）可使纹状体ACh释放呈剂量依赖性降低，而腹腔注射特异性DA D2受体拮抗剂舒必利则可使ACh释放呈剂量依赖性增加。相反，激动剂可使细胞外Ch水平升高，拮抗剂则使其降低。在舒必利处理的大鼠中观察到Ch摄取增加，而在N-434处理的大鼠中观察到Ch摄取减少。D2拮抗剂可完全拮抗D2激动剂对细胞外Ch、ACh和Ch摄取的影响。这些结果清楚地表明，D2受体激活可抑制ACh释放，这与先前关于DA-ACh相互作用的研究结果相反。细胞外Ch和ACh之间的反向关系反映了由于通过D2受体机制胆碱能神经元活动的变化而导致的Ch摄取的改变。
