Chen J P, Paredes W, Gardner E L
Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461.
Neurosci Lett. 1991 Jan 14;122(1):127-31. doi: 10.1016/0304-3940(91)90209-c.
As measured using in vivo brain microdialysis in conscious freely-moving rats, chronic treatment (20 mg/kg/day i.p. for 21 days) with the clinically atypical neuroleptic clozapine selectively reduced basal dopamine (DA) release in the nucleus accumbens (Acb) but not in caudate-putamen (CPu). Apomorphine (100 micrograms/kg s.c.) enhanced presynaptic Acb DA release in clozapine-treated rats, but reduced Acb DA release in vehicle-treated rats. These findings provide further evidence that depolarization block of mesolimbic DA neurons projecting to Acb but not of nigrostriatal DA neurons projecting to CPu may underlie clozapine's unusual clinical efficacy and its lack of production of extrapyramidal motoric effects.
在清醒自由活动大鼠中采用体内脑微透析法进行测量，用临床非典型抗精神病药物氯氮平进行慢性治疗（腹腔注射20毫克/千克/天，持续21天）可选择性降低伏隔核（Acb）中的基础多巴胺（DA）释放，但不会降低尾状核-壳核（CPu）中的基础多巴胺释放。阿扑吗啡（皮下注射100微克/千克）可增强氯氮平治疗大鼠突触前Acb DA的释放，但会降低溶剂治疗大鼠的Acb DA释放。这些发现进一步证明，投射到Acb的中脑边缘DA神经元的去极化阻滞而非投射到CPu的黑质纹状体DA神经元的去极化阻滞，可能是氯氮平不同寻常的临床疗效及其不产生锥体外系运动效应的基础。
