Wang Hui-Dong, Dunnavant Floyd D, Jarman Tabitha, Deutch Ariel Y
Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Neuropsychopharmacology. 2004 Jul;29(7):1230-8. doi: 10.1038/sj.npp.1300449.
The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.
成年哺乳动物大脑中新生细胞的产生可能会显著改变神经精神疾病中的病理生理过程。我们研究了用抗精神病药物（APD）奥氮平和氟哌啶醇进行长期治疗，对成年雄性大鼠前额叶皮质（PFC）和纹状体复合体中新生细胞数量和存活率的影响。给动物用奥氮平或氟哌啶醇治疗3周，然后注射5-溴-2'-脱氧尿苷（BrdU）标记有丝分裂细胞。在BrdU注射后，一半动物继续使用相同的APD再治疗两周，另一半在此期间接受赋形剂。奥氮平而非氟哌啶醇显著增加了PFC和背侧纹状体中BrdU标记细胞的总数和密度；伏隔核中未观察到影响。BrdU注射后继续使用奥氮平治疗并未增加新生细胞的存活率。PFC中的新生细胞不表达神经元标记NeuN。尽管奥氮平治疗的大鼠PFC中新生细胞显著增加，但这些细胞的总数较低，这表明非典型APD治疗的疗效可能并非归因于迁移至皮质的新生细胞的存在。
