Angulo J A, Cadet J L, McEwen B S
Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY.
Neurosci Lett. 1990 May 31;113(2):217-21. doi: 10.1016/0304-3940(90)90306-t.
A significant population of striatal neurons synthesize the tachykinin peptides substance P and neurokinin A. The synthesis of these neuropeptides is under tonic stimulation by dopaminergic neurotransmission. Since typical and atypical neuroleptic drugs display differential effects on the activity of dopaminergic neurons, we evaluated the effect of typical (haloperidol and prolixin) and atypical (molindone, thioridazine and chlozapine) chronic neuroleptic treatment on protachykinin mRNA levels in the medial aspect of the caudate-putamen by in situ hybridization histochemistry. Both typical and atypical neuroleptics decreased protachykinin mRNA levels by 22-40% relative to saline-injected controls. Clozapine failed to affect protachykinin mRNA levels. The data suggest the hypothesis that decreased striatal protachykinin mRNA levels may not be directly linked to development of extrapyramidal side effects.
大量纹状体神经元合成速激肽肽类物质P和神经激肽A。这些神经肽的合成受到多巴胺能神经传递的紧张性刺激。由于典型和非典型抗精神病药物对多巴胺能神经元的活性表现出不同的影响，我们通过原位杂交组织化学评估了典型（氟哌啶醇和丙氯拉嗪）和非典型（吗茚酮、硫利达嗪和氯氮平）慢性抗精神病治疗对尾状核-壳核内侧原速激肽mRNA水平的影响。与注射生理盐水的对照组相比，典型和非典型抗精神病药物均使原速激肽mRNA水平降低了22%-40%。氯氮平未能影响原速激肽mRNA水平。这些数据提示了一个假说，即纹状体原速激肽mRNA水平降低可能与锥体外系副作用的发生没有直接联系。
