Sherman K A, Hanin I, Zigmond M J
J Pharmacol Exp Ther. 1978 Sep;206(3):677-86.
It has previously been shown that neuroleptic drugs block an apparently inhibitory influence of dopamine on cholinergic interneurons in striatum, thereby increasing acetylcholine turnover. In this study, systemic administration of the neuroleptic, fluphenazine, decreased the acetylcholine content in the striatum but not the neocortex of rats killed by focussed microwave irradiation. The effect was observed with doses of fluphenazine as low as 0.05 mg/kg, and was also seen after two other neuroleptics, spiroperidol (1 mg/kg) and haloperidol (4 mg/kg). In contrast, neither fluphenazine nor haloperidol pretreatment had any effect on the high affinity accumulation of choline by striatal synaptosomes. These observations suggest that after administration of dopamine receptor antagonists the release and metabolism of acetylcholine in the striatum is increased, but that a compensatory increase in choline uptake does not occur, thereby resulting in a temporary decrease in acetylcholine concentration. On the basis of these findings, we conclude that acetylcholine synthesis is regulated differently in the striatum than in other brain regions.
先前的研究表明，抗精神病药物可阻断多巴胺对纹状体胆碱能中间神经元的明显抑制作用，从而增加乙酰胆碱的周转率。在本研究中，通过聚焦微波照射处死大鼠后，全身性给予抗精神病药物氟奋乃静可降低纹状体中的乙酰胆碱含量，但对新皮质中的乙酰胆碱含量无影响。在低至0.05mg/kg的氟奋乃静剂量下即可观察到该效应，其他两种抗精神病药物，即螺哌啶醇（1mg/kg）和氟哌啶醇（4mg/kg）给药后也可见到该效应。相比之下，氟奋乃静和氟哌啶醇预处理均对纹状体突触体摄取胆碱的高亲和力无任何影响。这些观察结果表明，给予多巴胺受体拮抗剂后，纹状体中乙酰胆碱的释放和代谢增加，但胆碱摄取未出现代偿性增加，从而导致乙酰胆碱浓度暂时降低。基于这些发现，我们得出结论，纹状体中乙酰胆碱的合成调控方式与其他脑区不同。
