Schmitt A, Weber S, Jatzko A, Braus D F, Henn F A
Central Institute of Mental Health, Mannheim, Germany.
J Neural Transm (Vienna). 2004 Jan;111(1):91-100. doi: 10.1007/s00702-003-0070-2. Epub 2003 Dec 3.
The dentate gyrus contains progenitor cells possessing the capacity to proliferate until and throughout adulthood. There is little information about the influence of antipsychotics on cell proliferation. To address this, we investigated the influence of acute and chronic haloperidol and clozapine treatment on the total number of newly dividing cells and hippocampal volume using an animal model with doses equivalent to the therapeutic range in humans. Rats were treated with either acute or 28 days haloperidol (1 mg/kg i.p. or 1,5 mg/kg/day oral) or clozapine (30 mg/kg i.p. or 45 mg/kg/day oral). After BrdU injection, immunohistochemistry was performed in serial hippocampal brain sections. Total BrdU-labeled cell number and hippocampus volume were estimated using stereological methods. Neither neuroleptic altered total number of newly dividing cells in the dentate gyrus. In contrast, chronic haloperidol treatment did increase total hippocampal volume suggesting that haloperidol alters neuroplastic processes or glial morphology rather than cell proliferation.
齿状回包含祖细胞，这些祖细胞具有增殖能力，可一直持续到成年期并在成年期全程保持这种能力。关于抗精神病药物对细胞增殖的影响，目前所知甚少。为了解决这个问题，我们使用一个动物模型，采用等同于人类治疗范围的剂量，研究了急性和慢性给予氟哌啶醇及氯氮平对新分裂细胞总数和海马体积的影响。大鼠分别接受急性或为期28天的氟哌啶醇（腹腔注射1毫克/千克或口服1.5毫克/千克/天）或氯氮平（腹腔注射30毫克/千克或口服45毫克/千克/天）治疗。注射溴脱氧尿苷（BrdU）后，对海马脑连续切片进行免疫组织化学分析。使用体视学方法估计BrdU标记细胞的总数和海马体积。两种抗精神病药物均未改变齿状回中新分裂细胞的总数。相反，慢性氟哌啶醇治疗确实增加了海马的总体积，这表明氟哌啶醇改变的是神经可塑性过程或神经胶质形态，而非细胞增殖。
