Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen.
Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen.
复制标题
5-羟色胺去神经增强了伏核中突触前多巴胺流出对急性氯氮平的反应性，但尾壳核中却没有。
DOI：
10.1016/0006-8993(92)90335-7
复制
发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Gardner,EL
中科院分区：
文献类型：
--
作者：
Chen,J;Paredes,W;vanPraag,HM;Gardner,EL
在实验动物中，氯氮平改变中脑边缘多巴胺（DA）功能，但保留黑质纹状体DA功能，但其潜在机制尚不清楚。在本研究中，急性腹腔注射氯氮平（5-40 mg/kg）增加细胞外DA水平在清醒的，自由活动的大鼠在体脑微透析测定，无解剖选择性的延髓核（Acb）和尾壳核（CPu）。然而，在5-羟色胺（5-HT）-去神经大鼠急性氯氮平优先增强DA水平的Acb相比，CPu。由于（i）DA神经元上5 HT受体的上调可能是由5 HT去神经支配引起的，（ii）氯氮平具有有效的抗5 HT作用，以及（iii）Acb中的5 HT受体比CPu中的5 HT受体更密集，这些数据似乎为先前的建议增加了额外的权重，即多巴胺能机制可能部分地构成氯氮平的中脑边缘选择性的基础。
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.