内侧前额叶皮质D2和纹状体边缘系统D4多巴胺受体：典型和非典型抗精神病药物的共同靶点。

Medial prefrontal cortical D2 and striatolimbic D4 dopamine receptors: common targets for typical and atypical antipsychotic drugs.

Tarazi F I, Yeghiayan S K, Neumeyer J L, Baldessarini R J

Consolidated Department of Psychiatry & Neuroscience Program, Harvard Medical School, Belmont, MA, USA.

Prog Neuropsychopharmacol Biol Psychiatry. 1998 May;22(4):693-707. doi: 10.1016/s0278-5846(98)00033-5.

Abstract

In vitro receptor autoradiography was used to examine the long-term effects of a typical (fluphenazine), atypical (clozapine), or potential atypical antipsychotic (S[+]-N-n-propylnorapomorphine; [+]-NPA) on different dopamine (DA) receptor subtypes. 2. D1-Like and D3 receptor levels were not changed with any treatment in any brain region examined. 3. D2 Receptors in caudate-putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OT) were significantly increased by long-term treatment with fluphenazine, but not with clozapine or S[+]-NPA. 4. D2 Receptor levels in medial prefrontal cortex (MPC), but not dorsolateral frontal cortex (DFC), were elevated after repeated daily administration of fluphenazine, clozapine, and S[+]-NPA. 5. D4-Like receptors, assayed under D4-selective conditions, were increased by fluphenazine, clozapine and S(+)-NPA in both NAc and CPu, but by none of these treatments in OT, DFC or MPC. 6. These results support a common role for medial prefrontal cortical D2 and striatolimbic D4 receptors in mediating the clinical actions of typical and atypical antipsychotic drugs.

摘要

采用体外受体放射自显影技术，研究典型抗精神病药物（氟奋乃静）、非典型抗精神病药物（氯氮平）或潜在非典型抗精神病药物（S[+]-N-正丙基去甲阿扑吗啡；[+]-NPA）对不同多巴胺（DA）受体亚型的长期影响。2. 在所有检测的脑区中，任何一种药物处理均未改变D1样受体和D3受体水平。3. 长期给予氟奋乃静可使尾状核-壳核（CPu）、伏隔核（NAc）和嗅结节（OT）中的D2受体显著增加，但氯氮平和S[+]-NPA无此作用。4. 每日重复给予氟奋乃静、氯氮平和S[+]-NPA后，内侧前额叶皮质（MPC）而非背外侧前额叶皮质（DFC）中的D2受体水平升高。5. 在D4选择性条件下检测的D4样受体，在NAc和CPu中，氟奋乃静、氯氮平和S(+)-NPA均可使其增加，但在OT、DFC或MPC中，这些药物处理均无此作用。6. 这些结果支持内侧前额叶皮质D2受体和纹状体边缘系统D4受体在介导典型和非典型抗精神病药物临床作用中具有共同作用。