Different effects of subchronic clozapine and haloperidol on dye-coupling between neurons in the rat striatal complex.
Different effects of subchronic clozapine and haloperidol on dye-coupling between neurons in the rat striatal complex.
复制标题
亚慢性氯氮平和氟哌啶醇对大鼠纹状体复合体神经元之间染料偶联的不同影响。
DOI：
10.1016/0306-4522(95)00091-v
复制
发表时间：
1995
期刊：
影响因子：
3.3
通讯作者：
Grace,AA
中科院分区：
文献类型：
--
作者：
O'Donnell,P;Grace,AA
非典型抗精神病药物，如氯氮平，与经典抗精神病药物(如氟哌啶醇)的区别在于，它们产生运动副作用的可能性较低。虽然初步研究表明抗精神病药物的临床疗效与它们与D2多巴胺受体的亲和力有关，但这些药物的治疗效果和锥体外系症状的延迟起效暗示了更复杂的作用机制。在这项研究中，我们发现，连续(但不是急性)使用任何一种药物的大鼠，在停药后，都会导致大鼠纹状体复合体边缘部分(即伏隔核壳区域)神经元之间的染料偶联增加。此外，持续的氟哌啶醇治疗，而不是氯氮平，也增加了纹状体复合体运动相关部分(即背侧纹状体)的染料偶联。因此，这两种治疗有效的药物对伏隔核壳内神经元之间的染料偶联显示出延迟效应，而只有与运动副作用相关的药物改变了背侧纹状体细胞之间的偶联。因此，抗精神病药物可能通过持续改变来自皮质的信号在这些大脑区域内整合的方式，来缓解精神分裂症患者认知功能的深刻障碍。
Atypical antipsychotic drugs, such as clozapine, are distinguished from classical antipsychotics (e.g. haloperidol) by their lower liability for producing motor side-effects. Although initial studies suggested that the clinical efficacy of antipsychotic drugs is related to their affinity for the D2dopamine receptor, the delayed onset of both the therapeutic effects and the extrapyramidal symptoms associated with these drugs implicates a more complex mechanism of action. In this study, we found that continuous (but not acute) treatment of rats with either drug caused an increase in dye coupling between neurons in the limbic component of the rat striatal complex (i.e. the shell region of the nucleus accumbens) after withdrawal of the drugs. Furthermore, continuous treatment with haloperidol, but not clozapine, also increased dye coupling in the motor-related part of the striatal complex (i.e. the dorsal striatum). Thus, both therapeutically effective drugs show a delayed effect on dye coupling between neurons in the accumbens shell, whereas only the drug associated with motor side effects altered coupling between cells in the dorsal striatum. Antipsychotic drugs may therefore alleviate the profound disturbances in cognitive function of schizophrenics by producing sustained alterations in the way signals from the cortex are integrated within these brain regions.