Lane R F, Blaha C D, Rivet J M
Institute of Neuroscience, University of Oregon, Eugene 97403.
Brain Res. 1988 Sep 20;460(2):398-401. doi: 10.1016/0006-8993(88)90390-3.
The release of dopamine (DA) in vivo was compared in the striatum and nucleus accumbens following chronic (21 day) administration of clozapine (CLOZ) and repeated coadministration of haloperidol (HAL) and the alpha 1-noradrenergic (NE) receptor antagonist prazosin. Treatment with HAL reduced basal DA release in both brain regions, whereas treatment with CLOZ decreased basal DA release only in the accumbens. Chronic coadministration of HAL and prazosin resulted in decreased DA release in accumbens but not striatum. These results suggest that the alpha 1-NE receptor blocking properties of CLOZ may, in part, mediate its differential actions on nigrostriatal and mesolimbic DA release, an effect which may in addition contribute to its paucity of extrapyramidal side effects.
比较了长期（21天）给予氯氮平（CLOZ）以及反复联合给予氟哌啶醇（HAL）和α1-去甲肾上腺素能（NE）受体拮抗剂哌唑嗪后，纹状体和伏隔核中多巴胺（DA）在体内的释放情况。用HAL治疗可降低两个脑区的基础DA释放，而用CLOZ治疗仅降低伏隔核中的基础DA释放。长期联合给予HAL和哌唑嗪导致伏隔核中DA释放减少，但纹状体中未减少。这些结果表明，CLOZ的α1-NE受体阻断特性可能部分介导了其对黑质纹状体和中脑边缘DA释放的不同作用，这种作用可能还导致其锥体外系副作用较少。
