The effect of chronic haloperidol treatment on dendritic spines in the rat striatum
The effect of chronic haloperidol treatment on dendritic spines in the rat striatum
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DOI：
10.1006/exnr.1997.6552
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发表时间：
1997-08-01
影响因子：
5.3
通讯作者：
Roberts, RC
中科院分区：
文献类型：
--
作者：
Kelley, JJ;Gao, XM;Roberts, RC
先前的研究表明，与对照组相比，精神分裂症患者的皮质脊椎密度降低，纹状体脊椎变小。目前在大鼠身上进行的这项研究是为了确定这种差异是否可能是慢性抗精神病药物治疗的结果，以及它们是否与抗精神病药物诱导的口腔运动障碍有关。大鼠每天给予1.5 mg/kg氟哌啶醇(HA)(n=28)或水(n=10)，测试大鼠的空腹咀嚼运动(VCM)。6个月后，将大鼠分为低VCM组和高VCM组，除7只高VCM大鼠外，其余均处死。这些大鼠(撤退组)从HA撤除4周。对纹状体的随机电子显微照片进行分析，以了解脊椎的变化。透明质酸对脊柱大小无显著影响(0.193比0.174微米(2)，透明质酸和对照组分别为0.174微米(2))，也与口腔运动障碍(0.191微米(2)比0.196微米(2)，低和高氯乙烯浓度组)无显著相关性。这些结果表明，精神分裂症纹状体中较小的脊椎可能与疾病有关，而不是由抗精神病药物治疗引起的。与对照组(53·7±-7·3，P<；0.001)相比，HA治疗组脊柱密度降低(32·7±-9·5)，停药组脊柱密度仍较低(35·0±-4·2，P<；0·01)。与对照组相比，低(37.3+/-9.9，P<；0.01)和高(28.0+/-7.0，P<；0.000)组的脊柱密度也降低。然而，高VCM组和低VCM组之间没有显著差异，这表明脊柱密度的下降与口腔运动障碍无关。这些结果表明，精神分裂症皮质中观察到的脊椎密度下降可能是抗精神病药治疗的结果。(C)1997年学术出版社。
Previous studies have shown that schizophrenics, in comparison to controls, have reduced cortical spine density and smaller striatal spines. The current study in the rat was conducted to determine whether such differences could result from chronic neuroleptic treatment and whether they are correlated with neuroleptic-induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n = 28) or water (n = 10) were tested for vacuous chewing movements (VCMs). After 6 months, rats were divided into low and high VCM groups; all but seven high VCM rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4 weeks. Random electron micrographs of the striatum were analyzed for spine changes. Spine size was not significantly affected by HA (0.193 vs 0.174 mu m(2), HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs 0.196 mu m(2), low and high VCM groups, respectively). These results suggest that smaller spines in schizophrenic striatum may be correlated with the disease rather than caused by neuroleptic treatment. Spine density decreased in the HA-treated group (32.7 +/- 9.5) in comparison to controls (53.7 +/- 7.3, P < 0.001) and remained low in the withdrawn group (35.0 +/- 4.2, P < 0.01). Spine density also decreased in both the low (37.3 +/- 9.9, P < 0.01) and the high (28.0 +/- 7.0, P < 0.000) VCM groups in comparison to controls. However, there was no significant difference between high and low VCM groups, suggesting that decreased spine density is independent of oral dyskinesias. These results suggest that the decreased spine density observed in schizophrenic cortex may be a result of neuroleptic treatment. (C) 1997 Academic Press.