Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats
Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats
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DOI：
10.1016/j.neuropharm.2006.08.025
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Terry, Alvin V., Jr.
中科院分区：
文献类型：
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作者：
Hohnadel, Elizabeth;Bouchard, Kristy;Terry, Alvin V., Jr.
Acetylcholinesterase inhibitors (AChEIs) are currently being evaluated as adjunctive therapy for the cognitive dysfunction of schizophrenia.精神分裂症的这一核心症状通常归因于注意力受损和感觉运动门控异常，这些特征也存在于亨廷顿舞蹈病、自闭症和其他几种精神和神经疾病中。 The ability to improve prepulse inhibition (PPI) of the acoustic startle response may predict the efficacy of compounds as cognitive enhancers.在这项研究中，Wistar 大鼠的 PPI 在三种药理学模型中被破坏：阿朴吗啡的多巴胺受体激动作用、MK801 的 NMDA 受体拮抗作用或东莨菪碱的毒蕈碱乙酰胆碱受体拮抗作用。然后，我们评估了常用的 AChEI、多奈哌齐（0.5、1.0 或 2.0 mg/kg）和加兰他敏（0.3、1.0 或 3.0 mg/kg）在每个模型中改善 PPI 的能力。在车辆条件下，前脉冲刺激（75、80 和 85 dB）以分级方式抑制对 120 dB 听觉刺激的惊吓反应。加兰他敏（取决于剂量）改善了所有三种 PPI 破坏模型中的 PPI 缺乏，而多奈哌齐改善了东莨菪碱和阿朴吗啡引起的 PPI 缺乏，但在 MK801 模型中无效。 These results indicate that some AChEIs may have the potential to improve cognition in schizophrenia by improving auditory sensory gating. (c) 2006 Elsevier Ltd. 保留所有权利。
Acetylcholinesterase inhibitors (AChEIs) are currently being evaluated as adjunctive therapy for the cognitive dysfunction of schizophrenia. This core symptom of schizophrenia has often been attributed to impaired attention and abnormal sensory motor gating, features that are also found in Huntington's Disease, autism, and several other psychiatric and neurological disorders. The ability to improve prepulse inhibition (PPI) of the acoustic startle response may predict the efficacy of compounds as cognitive enhancers. In this study, PPI was disrupted in Wistar rats in three pharmacologic models: dopamine receptor agonism by apomorphine, NMDA receptor antagonism by MK801, or muscarinic acetylcholine receptor antagonism by scopolamine. We then evaluated the commonly used AChEIs, donepezil (0.5, 1.0, or 2.0 mg/kg) and galantamine (0.3, 1.0, or 3.0 mg/kg) for the capacity to improve PPI in each model. Under vehicle conditions, the prepulse stimuli (75, 80 and 85 dB) inhibited the startle response to a 120 dB auditory stimulus in a graded fashion. Galantamine (depending on dose) improved PPI deficits in all three PPI disruption models, whereas donepezil ameliorated PPI deficits induced by scopolamine and apomorphine, but was not effective in the MK801 model. These results indicate that some AChEIs may have the potential to improve cognition in schizophrenia by improving auditory sensory gating. (c) 2006 Elsevier Ltd. All rights reserved.