5-羟色胺去神经支配增强伏隔核中突触前多巴胺外流对急性氯氮平的反应性，但在尾状核-壳核中则不然。

Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen.

作者信息

Chen J, Paredes W, van Praag H M, Gardner E L

机构信息

Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461.

出版信息

Brain Res. 1992 Jun 5;582(1):173-9. doi: 10.1016/0006-8993(92)90335-7.

DOI:10.1016/0006-8993(92)90335-7

PMID:1379872

Abstract

Clozapine alters mesolimbic dopamine (DA) function but spares nigrostriatal DA function in laboratory animals, but the underlying mechanism is unknown. In the present study, acute intraperitoneal injection of clozapine (5-40 mg/kg) increased extracellular DA levels in nucleus accumbens (Acb) and caudate-putamen (CPu) of awake, freely moving rats as measured by in vivo brain microdialysis, without anatomic selectivity. However, in serotonin (5HT)-denervated rats acute clozapine preferentially enhanced DA levels in Acb as compared to CPu. Since (i) up-regulation of 5HT receptors on DA neurons may result from 5HT denervation, (ii) clozapine has potent anti-5HT action, and (iii) 5HT receptors are more dense in Acb than CPu, these data appear to add additional weight to previous suggestions that a serotonergic mechanism may partly underlie clozapine's mesolimbic selectivity.

摘要

氯氮平可改变实验动物中脑边缘多巴胺（DA）功能，但不影响黑质纹状体DA功能，但其潜在机制尚不清楚。在本研究中，通过体内脑微透析测量，急性腹腔注射氯氮平（5 - 40mg/kg）可增加清醒、自由活动大鼠伏隔核（Acb）和尾状核-壳核（CPu）的细胞外DA水平，无解剖学选择性。然而，在5-羟色胺（5HT）去神经支配的大鼠中，与CPu相比，急性氯氮平优先提高了Acb中的DA水平。由于（i）DA神经元上5HT受体的上调可能源于5HT去神经支配，（ii）氯氮平具有强大的抗5HT作用，以及（iii）5HT受体在Acb中比在CPu中更密集，这些数据似乎进一步支持了先前的观点，即5-羟色胺能机制可能部分是氯氮平中脑边缘选择性的基础。