Chen J, Paredes W, van Praag H M, Gardner E L
Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461.
Brain Res. 1992 Jun 5;582(1):173-9. doi: 10.1016/0006-8993(92)90335-7.
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.
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。
