Moghaddam B, Bunney B S
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
J Neurochem. 1990 May;54(5):1755-60. doi: 10.1111/j.1471-4159.1990.tb01230.x.
In vivo microdialysis has been used to study the acute effects of antipsychotic drugs on the extracellular level of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. (-)-Sulpiride (20, 50, and 100 mg/kg i.v.) and haloperidol (0.1 and 0.5 mg/kg i.v.) enhanced the outflow of dopamine in the striatum and nucleus accumbens. In the medial prefrontal cortex, (-)-sulpiride at all doses tested did not significantly affect the extracellular level of dopamine. The effect of haloperidol was also attenuated in the medial prefrontal cortex; 0.1 mg/kg did not increase the outflow of dopamine and the effect of 0.5 mg/kg haloperidol was of shorter duration in the prefrontal cortex than that observed in striatum and nucleus accumbens. The atypical antipsychotic drug clozapine (5 and 10 mg/kg) increased the extracellular concentration of dopamine in all three regions. In contrast to the effects of sulpiride and haloperidol, that of clozapine in the medial prefrontal cortex was profound. These data suggest that different classes of antipsychotic drugs may have distinct effects on the release of dopamine from the nigrostriatal, mesolimbic, and mesocortical terminals.
体内微透析已被用于研究抗精神病药物对大鼠伏隔核、纹状体和前额叶皮质细胞外多巴胺水平的急性影响。（-）舒必利（20、50和100mg/kg静脉注射）和氟哌啶醇（0.1和0.5mg/kg静脉注射）可增强纹状体和伏隔核中多巴胺的流出。在额叶内侧皮质，所有测试剂量的（-）舒必利均未显著影响多巴胺的细胞外水平。氟哌啶醇在额叶内侧皮质的作用也减弱；0.1mg/kg未增加多巴胺的流出，0.5mg/kg氟哌啶醇在额叶皮质的作用持续时间比在纹状体和伏隔核中观察到的要短。非典型抗精神病药物氯氮平（5和10mg/kg）增加了所有三个区域中多巴胺的细胞外浓度。与舒必利和氟哌啶醇的作用相反，氯氮平在额叶内侧皮质的作用显著。这些数据表明，不同类别的抗精神病药物可能对黑质纹状体、中脑边缘和中脑皮质终末的多巴胺释放有不同的影响。
