Lithium and valproate prevent olfactory discrimination and short-term memory impairments in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of Parkinson's disease
Lithium and valproate prevent olfactory discrimination and short-term memory impairments in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of Parkinson's disease
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DOI：
10.1016/j.bbr.2012.01.016
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发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Prediger, Rui D. S.
中科院分区：
文献类型：
--
作者：
Castro, Adalberto A.;Ghisoni, Karina;Prediger, Rui D. S.
我们最近已经证明，啮齿动物鼻内治疗与1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）显示时间依赖性的嗅觉，情感，认知和运动功能的损害与多巴胺能神经传递的中断在不同的大脑结构中，可以想象类似于在帕金森病（PD）的不同阶段观察到的。另一方面，锂（Li）和丙戊酸盐（VPA）是用于治疗双相情感障碍的两种主要药物，最近成为有前途的神经保护剂。目前的数据表明，连续7天腹腔注射Li（47.5 mg/kg）或VPA（200 mg/kg）能够预防大鼠在社会识别和降压抑制回避任务中评估的嗅觉辨别和短期记忆障碍。给予MPTP（0.1 mg/ml）。尽管在当前MPTP剂量后没有明显的抑郁样反应，但Li和VPA治疗呈现出抗抑郁特征，减少了强迫游泳试验中的不动时间。重要的是，此时在旷场试验中未观察到动物运动活性的显著变化。而且。Li和VPA可防止MPTP灌注大鼠的嗅球和纹状体中的多巴胺耗竭。这些结果为PD的实验模型提供了新的见解，表明Li和VPA可能代表了新的治疗工具，用于管理与PD早期临床前阶段相关的嗅觉和认知症状，以及先前研究中证明的神经保护潜力。(C)2012 Elsevier B. V.保留所有权利。
We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyL-1,2,3,6-tetrahydropyridine (MPTP) display time-dependent impairments in olfactory, emotional, cognitive and motor functions associated with disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, lithium (Li) and valproate (VPA) are two primary drugs used to treat bipolar mood disorder that have recently emerged as promising neuroprotective agents. The present data indicates that the pretreatment with Li (47.5 mg/kg) or VPA (200 mg/kg) by intraperitoneal route during 7 consecutive days was able to prevent olfactory discrimination and short-term memory impairments evaluated in the social recognition and step-down inhibitory avoidance tasks in rats infused with a single intranasal (in.) administration of MPTP (0.1 mg/nostril). Despite the absence of clear depressive-like responses following the current MPTP dose, Li and VPA treatment presented an antidepressant profile reducing the immobility time in the forced swimming test Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover. Li and VPA prevented dopamine depletion in the olfactory bulb and striatum of MPTP-infused rats. These results provide new insights in experimental models of PD, indicating that Li and VPA may represent new therapeutic tools for the management of olfactory and cognitive symptoms associated to early preclinical phases of PD, together with their neuroprotective potential demonstrated in previous research. (C) 2012 Elsevier B.V. All rights reserved.