Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging
Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging
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DOI：
10.1016/j.nucmedbio.2014.04.133
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发表时间：
2014-09-01
影响因子：
3.1
通讯作者：
Chang, K. W.
中科院分区：
文献类型：
--
作者：
Huang, Y. R.;Pai, C. W.;Chang, K. W.
前言：EpidePride是一种与D-2/D-3受体具有皮摩尔亲和力的化合物。本工作旨在探讨[I-123]epidePride成像平台对利培酮治疗慢性MK-801诱导的大鼠精神分裂症模型的诊断可能性。方法：大鼠重复给予MK-801(溶于生理盐水，每天0.3 mg/kg)或生理盐水4周。MK-801给药1周后，MK-801+利培酮组在给药前15min给予利培酮(0.5 mg/kg/d)，继续给药3周。结果：利培酮逆转了MK-801所致的慢性社会交往时间的缩短。IHC和ELISA法分析结果显示，慢性MK-801治疗显著降低了纹状体和中脑D2R的表达，但重复利培酮治疗逆转了MK-801治疗的作用。此外，[I-123]epidePride纳米SPECT/CT神经成像显示，MK-801在纹状体和中脑引起的低特异性epidePride结合率在利培酮治疗1周和2周后分别有统计学意义的缓解。结论：MK-801慢性给药4周可建立大鼠精神分裂症模型。[I-123]EpidePride纳米SPECT神经成像可以追踪长期使用MK-801治疗引起的纹状体和中脑D2R表达的进行性变化。在慢性MK-801诱导的大鼠精神分裂症模型中，除了诊断疾病阶段外，[I-123]epidePride还可以作为评估抗精神病药物疗效的有用工具。(C)2014 Elsevier Inc.保留所有权利。
Introduction: Epidepride is a compound with an affinity in picomolar range for D-2/D-3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [I-123]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model.Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3 mg/kg/day) or saline for 4 weeks. After 1-week administration of MK-801, rats in MK-801 + risperidone group received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [I-123]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain.Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration.IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D2R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [I-123]epidepride nanoSPECT/CT neuroimaging revealed that low specific [I-123]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively.Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4 weeks. [I-123] Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D2R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [I-123] epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model. (C) 2014 Elsevier Inc. All rights reserved.