非典型抗精神病药物可选择性地增加多巴胺终末区域的神经降压素流出。
Atypical antipsychotic drugs selectively increase neurotensin efflux in dopamine terminal regions.
作者信息
Radke J M, Owens M J, Ritchie J C, Nemeroff C B
机构信息
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11462-4. doi: 10.1073/pnas.95.19.11462.
Abstract
Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo microdialysis, we now report that acute administration of haloperidol, clozapine, or olanzapine failed to alter the release of NT in either the striatum or nucleus accumbens. In contrast, chronic administration of haloperidol for 21 days increased NT release in both the striatum and nucleus accumbens, whereas treatment for 21 days with the atypical antipsychotic drugs, clozapine or olanzapine, increased NT release selectively in the nucleus accumbens. These findings suggest that (i) increased NT mRNA expression and NT tissue concentrations are associated with increases in the extracellular fluid concentrations of the peptide and (ii) atypical antipsychotic drugs may exert their therapeutic effects and produce fewer side effects by virtue of their selectivity in limbic compared with striatal, target neurons.
摘要
典型抗精神病药物，如氟哌啶醇和氯丙嗪，会增加纹状体和伏隔核中神经肽神经降压素（NT）的合成，而非典型抗精神病药物，如氯氮平和奥氮平，则仅在伏隔核中增加其合成。通过体内微透析技术，我们现在报告，急性给予氟哌啶醇、氯氮平或奥氮平不会改变纹状体或伏隔核中NT的释放。相反，连续21天给予氟哌啶醇会增加纹状体和伏隔核中NT的释放，而连续21天给予非典型抗精神病药物氯氮平或奥氮平，则仅选择性地增加伏隔核中NT的释放。这些发现表明：（i）NT信使核糖核酸（mRNA）表达增加和NT组织浓度升高与该肽细胞外液浓度增加相关；（ii）与纹状体靶神经元相比，非典型抗精神病药物对边缘系统靶神经元具有选择性，这可能是其发挥治疗作用并产生较少副作用的原因。
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